Dave Atherton adds his thoughts:
I thought it must be my turn to add something to the debate on smoking and lung cancer. I personally believe the inhalation of tobacco smoke to the lungs is a direct cause of lung cancer. With relative risks RR of between 9 to 20 there is overwhelming epidemiological and as I hope to prove scientific evidence that directly leads to growth of tumours on lungs. Also it very much seems to be dose respondent in that the more you smoke the greater the risk. For example the Neuberger paper from 2006 puts the risk at "The major risk factor for lung cancer is cigarette smoking, with a relative risk of 20 to 25 and an attributable risk of 85 to 90 percent." However the Neuberger paper also found the passive smoking incidence of lung cancer to be the inverse. "A significant inverse association was found …for those with adult passive smoke exposure at home (OR=0.37, 95% CI=0.26-0.54)." I also note in the Neuberger paper that "Urban residence was a significantly increased risk factor using inside city limits as the category (OR=1.84, 95% CI=1.35-2.51)."
The basic scientific reason for lung cancer in active smokers is genetic mutation caused by smoking. All us have on chromosome 17 the tumor protein gene 53 or p53. Its function "p53 is important in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer. As such, p53 has been described as "the guardian of the genome", the "guardian angel gene", and the "master watchman", referring to its role in conserving stability by preventing genome mutation. " Putting it simply it stops cancer cells dividing.
When you smoke the burning of tobacco produces tar (the tar dissolves the nicotine) causes benzo(a)pyrene to be produced. Benzo(a)pyrence is a 5 ring benzene molecule and benzene is a Group 1 carcinogen and proven cause of cancer. The inhalation of benzo(a)pyrene causes a guanine to thymine transversion where within the DNA of the p53 gene the guanine and tymine molecules change position within the helix of the DNA rendering the p53 inert and the onco (cancer) gene K ras allows the cancer cells to develop. That medically and scientifically is the reason that smoking directly causes lung cancer.
However on passive smoking this very research proves that second hand smoke (ETS) does not cause lung cancer in non smokers. In non smokers it is the mutilation of the epidermal growth factor receptor (EPGR) gene that causes lung cancer. This is from a paper form Professor Aslaug Helland in 2009, "The K-Ras-gene is often mutated in tumours from smokers, but seldom in tumours from non-smokers; whereas the EGFR-gene is mutated in tumours from non-smokers, and not in smokers…. INTERPRETATION: Lung cancer in never-smokers should probably be regarded as a different disease-entity than smoking-induced lung cancer."
What I find particularly offensive is that the WHO/IRAC also know all too well that this is the case too. In 2003 they produced this paper which was to finally confirm the direct link between smoking and lung cancer. Of course they scored an own goal in that they also proved that passive smoking does not cause lung cancer in non smokers. "In 1998, Pierre Hainaut and his collaborators at IARC analyzed the mutations in lung cancers that were at the time in the IARC p53 database. They found that the positions of damage by benzo(a)pyrene spotted by Pfeifer and his team were frequently the sites of mutations in lung cancers of smokers but rarely in lung cancers of non-smokers." Robert Nilsson wrote in 2003 too "The one-sided preoccupation with ETS as a causative factor of lung cancer in non-smokers may seriously hinder the elucidation of the multifactorial etiology of these tumors…..This goal can be achieved, however, without the introduction of an extremist legislation based on a negligible risk of lung cancer as well as an unsupported and highly hypothetical risk for CHD."
The reason why ex smokers are at risk and have much higher rates of lung cancer is that once a gene is mutated the p24 gene is unable to repair the DNA damage. While smokers continue to damage their p53 gene by continually smoking the damage with non smokers stabilises.
So in conclusion I do believe that smoking causes lung cancer, the science is persuasive.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1876736/
http://en.wikipedia.org/wiki/P53
http://en.wikipedia.org/wiki/Benzo(a)pyrene
http://www.ncbi.nlm.nih.gov/pubmed/11389059
http://www.ncbi.nlm.nih.gov/pubmed/19844277
Frank Davis 
Sagawa – Kyobu Geka 1995 abstract / PubMed
Human papillomavirus DNA and TP53 mutations in lung cancers from butchers. AA al-Ghamdi, CM Sanders, M Keefe, D Coggon, NJ Maitland. Br J Cancer 1995 Aug;72(2):293-297. 1/8 squamous cell carcinomas were HPV positive; types 16, 18 and 33 were tested for by PCR.
al-Ghamdi – Br J Cancer 1995 abstract / PubMed
Detection of human papillomavirus types 16, 18 DNA related sequences in bronchogenic carcinoma by polymerase chain reaction. Q Li, K Hu, X Pan, Z Cao, J Yang, S Hu. Chin Med J (Engl) 1995 Aug;108(8):610-614. “HPV 16, 18 DNA related sequences were found in 32% of lung cancer specimens, with 10 cases of HPV 16, 5 cases of HPV 18 and 1 case of both types. 48.15% (13/27) of squamous cell carcinomas were shown to be positive for HPV 16, 18 DNA. In addition, two adenocarcinomas and one small cell carcinoma were positive for HPV 16 DNA. No specimens from benign diseases tissues and fetal lung tissues showed positive results. These results suggest that primary bronchogenic carcinoma is related to HPV infection.”
Li – Chin Med J (Engl) 1995 abstract / PubMed
[Point mutation of p53 and detection of human papillomavirus DNA in bronchogenic carcinoma]. X Zhang, Y Zhu, L Li. Zhonghua Nei Ke Za Zhi 1995 Oct;34(10):673-675. 4/34 HPV+, all 4 were squamous cell; HPV types tested for were not specified in the abstract.
Zhang – Zhonghua Nei Ke Za Zhi 1995 abstract / PubMed
Detection of human papillomavirus DNA in primary lung carcinoma by nested polymerase chain reaction. P Thomas, X De Lamballerie, L Garbe, H Douagui, JP Kleisbauer. Cell Mol Biol (Noisy-le-grand) 1995 Dec;41(8):1093-1097. Types 6/11, 16 and 18 found in 2/18 (11%) of squamous cell, 1/4 adenocarcinomas, 2/7 neuroendocrine, 0/2 large cell.
Thomas – Cell Mol Biol (Noisy-le-grand) 1995 abstract / PubMed
p53 protein accumulation and the presence of human papillomavirus DNA in bronchiolo-alveolar carcinoma correlate with poor prognosis. K Nuorva, Y Soini, D Kamel, R Pollanen, R Bloigu, K Vahakangas, P Paakko. Int J Cancer 1995 Dec 20;64(6):424-429. HPV types 6, 11, 16, 18, 31, and 33 were tested for; 36% (8) of 22 bronchiolo-alveolar carcinomas were positive.
Sagawa – Kyobu Geka 1995 abstract / PubMed
Human papillomavirus DNA and TP53 mutations in lung cancers from butchers. AA al-Ghamdi, CM Sanders, M Keefe, D Coggon, NJ Maitland. Br J Cancer 1995 Aug;72(2):293-297. 1/8 squamous cell carcinomas were HPV positive; types 16, 18 and 33 were tested for by PCR.
al-Ghamdi – Br J Cancer 1995 abstract / PubMed
Detection of human papillomavirus types 16, 18 DNA related sequences in bronchogenic carcinoma by polymerase chain reaction. Q Li, K Hu, X Pan, Z Cao, J Yang, S Hu. Chin Med J (Engl) 1995 Aug;108(8):610-614. “HPV 16, 18 DNA related sequences were found in 32% of lung cancer specimens, with 10 cases of HPV 16, 5 cases of HPV 18 and 1 case of both types. 48.15% (13/27) of squamous cell carcinomas were shown to be positive for HPV 16, 18 DNA. In addition, two adenocarcinomas and one small cell carcinoma were positive for HPV 16 DNA. No specimens from benign diseases tissues and fetal lung tissues showed positive results. These results suggest that primary bronchogenic carcinoma is related to HPV infection.”
Li – Chin Med J (Engl) 1995 abstract / PubMed
[Point mutation of p53 and detection of human papillomavirus DNA in bronchogenic carcinoma]. X Zhang, Y Zhu, L Li. Zhonghua Nei Ke Za Zhi 1995 Oct;34(10):673-675. 4/34 HPV+, all 4 were squamous cell; HPV types tested for were not specified in the abstract.
Zhang – Zhonghua Nei Ke Za Zhi 1995 abstract / PubMed
Detection of human papillomavirus DNA in primary lung carcinoma by nested polymerase chain reaction. P Thomas, X De Lamballerie, L Garbe, H Douagui, JP Kleisbauer. Cell Mol Biol (Noisy-le-grand) 1995 Dec;41(8):1093-1097. Types 6/11, 16 and 18 found in 2/18 (11%) of squamous cell, 1/4 adenocarcinomas, 2/7 neuroendocrine, 0/2 large cell.
Thomas – Cell Mol Biol (Noisy-le-grand) 1995 abstract / PubMed
p53 protein accumulation and the presence of human papillomavirus DNA in bronchiolo-alveolar carcinoma correlate with poor prognosis. K Nuorva, Y Soini, D Kamel, R Pollanen, R Bloigu, K Vahakangas, P Paakko. Int J Cancer 1995 Dec 20;64(6):424-429. HPV types 6, 11, 16, 18, 31, and 33 were tested for; 36% (8) of 22 bronchiolo-alveolar carcinomas were positive.
Nuorva / Int J Cancer 1995 abstract / PubMed
[Human papillomavirus infection and p53 gene mutation in primary lung cancer]. J Da, L Chen, Y Hu. Zhonghua Zhong Liu Za Zhi 1996 Jan;18(1):27-29. “HPV-DNA positive rate in lung cancer was 55% (22/40 cases), including SCLC (9/9 cases), squamous cell carcinomas (8/16 cases), and adenocarcinomas (5/12 cases)…. SCLC and squamous carcinoma had higher HPV infection rate than other types of lung cancer.”
Da – Zhonghua Zhong Liu Za Zhi 1996 abstract / PubMed
Detection of human papilloma virus (HPV) and K-ras mutations in human lung carcinomas. A Noutsou, M Koffa, M Ergazaki, et al. Int J Oncol 1996;8:1089–1093. No abstract. Reported in Syrjanen 2001: 8 out of 41 (20%) adenocarcinomas were positive for HPV (2 type 16, 6 type 18) by PCR.
Presence of human papillomavirus DNA and abnormal p53 protein accumulation in lung carcinoma. Y Soini, K Nuorva, D Kamel, R Pollanen, K Vahakangas, VP Lehto, P Paakko. Thorax 1996 Sep;887-893. HPV types 6, 11, 16, 18, 31, and 33 were tested for, 13/43 (30%) were positive, tumor types not stated in the abstract.
Soini – Thorax 1996 abstract / PubMed
Human papillomavirus DNA in squamous cell carcinoma of the lung. T Hirayasu, T Iwamasa, Y Kamada, Y Koyanagi, H Usuda, K Genka. J Clin Pathol 1996 Oct;49(10):810-817. Higher percentage of HPV+ in Okinawa than Niigata (79% versus 30% by PCR), despite similar smoking rates. “The detection of HPV DNA was strongly associated with well differentiated SCC. This was particularly true for HPV types 6 and 16. There was no correlation between either smoking and detection of HPV DNA, or smoking and histological differentiation.”
Hirayasu – J Clin Pathol 1996 abstract / PubMed
[Detection of human papillomavirus by polymerase chain reaction in primary lung carcinoma]. P Thomas, X De Lamballerie, L Garbe, O Castelnau, JP Kleisbauer. Bull Cancer 1996 Oct;83(10):842-846. HPV types 6/11, 16 and 18 were found in 2/18 (11%) of squamous cell, 1/4 adenocarcinomas, 1/6 small cell, and 1/1 neuroendocrine carcinomas.
Thomas – Bull Cancer 1996 abstract / PubMed
Human papillomavirus infection is not associated with bronchial carcinoma: evaluation by in situ hybridization and the polymerase chain reaction. A Welt, M Hummel, G Niedobitek, H Stein. J Pathol 1997 Mar;181(3):276-280. 0 of 38 (32 squamous cell carcinomas (SCCs) and six small cell carcinomas of the bronchus) were positive for HPV types 6, 11, 16 or 18 by PCR and ISH.
Welt – J Pathol 1997 abstract / PubMed
Carcinoma of the lung in Okinawa, Japan: with special reference to squamous cell carcinoma and squamous metaplasia. I Nakazato, T Hirayasu, Y Kamada, K Tsuhako, T Iwamasa. Pathol Int 1997 Oct;47(10):659-672. “The authors postulate that HPV infects adenocarcinoma cells and changes them to enlarged cells, followed by squamous metaplasia. In this report, HPV DNA was transfected to adenocarcinoma cells (cultured cell lines) and this showed that HPV causes squamous metaplasia.”
Nakazato – Pathol Int 1997 abstract / PubMed
Nuorva / Int J Cancer 1995 abstract / PubMed
[Human papillomavirus infection and p53 gene mutation in primary lung cancer]. J Da, L Chen, Y Hu. Zhonghua Zhong Liu Za Zhi 1996 Jan;18(1):27-29. “HPV-DNA positive rate in lung cancer was 55% (22/40 cases), including SCLC (9/9 cases), squamous cell carcinomas (8/16 cases), and adenocarcinomas (5/12 cases)…. SCLC and squamous carcinoma had higher HPV infection rate than other types of lung cancer.”
Da – Zhonghua Zhong Liu Za Zhi 1996 abstract / PubMed
Detection of human papilloma virus (HPV) and K-ras mutations in human lung carcinomas. A Noutsou, M Koffa, M Ergazaki, et al. Int J Oncol 1996;8:1089–1093. No abstract. Reported in Syrjanen 2001: 8 out of 41 (20%) adenocarcinomas were positive for HPV (2 type 16, 6 type 18) by PCR.
Presence of human papillomavirus DNA and abnormal p53 protein accumulation in lung carcinoma. Y Soini, K Nuorva, D Kamel, R Pollanen, K Vahakangas, VP Lehto, P Paakko. Thorax 1996 Sep;887-893. HPV types 6, 11, 16, 18, 31, and 33 were tested for, 13/43 (30%) were positive, tumor types not stated in the abstract.
Soini – Thorax 1996 abstract / PubMed
Human papillomavirus DNA in squamous cell carcinoma of the lung. T Hirayasu, T Iwamasa, Y Kamada, Y Koyanagi, H Usuda, K Genka. J Clin Pathol 1996 Oct;49(10):810-817. Higher percentage of HPV+ in Okinawa than Niigata (79% versus 30% by PCR), despite similar smoking rates. “The detection of HPV DNA was strongly associated with well differentiated SCC. This was particularly true for HPV types 6 and 16. There was no correlation between either smoking and detection of HPV DNA, or smoking and histological differentiation.”
Hirayasu – J Clin Pathol 1996 abstract / PubMed
[Detection of human papillomavirus by polymerase chain reaction in primary lung carcinoma]. P Thomas, X De Lamballerie, L Garbe, O Castelnau, JP Kleisbauer. Bull Cancer 1996 Oct;83(10):842-846. HPV types 6/11, 16 and 18 were found in 2/18 (11%) of squamous cell, 1/4 adenocarcinomas, 1/6 small cell, and 1/1 neuroendocrine carcinomas.
Thomas – Bull Cancer 1996 abstract / PubMed
Human papillomavirus infection is not associated with bronchial carcinoma: evaluation by in situ hybridization and the polymerase chain reaction. A Welt, M Hummel, G Niedobitek, H Stein. J Pathol 1997 Mar;181(3):276-280. 0 of 38 (32 squamous cell carcinomas (SCCs) and six small cell carcinomas of the bronchus) were positive for HPV types 6, 11, 16 or 18 by PCR and ISH.
Welt – J Pathol 1997 abstract / PubMed
Carcinoma of the lung in Okinawa, Japan: with special reference to squamous cell carcinoma and squamous metaplasia. I Nakazato, T Hirayasu, Y Kamada, K Tsuhako, T Iwamasa. Pathol Int 1997 Oct;47(10):659-672. “The authors postulate that HPV infects adenocarcinoma cells and changes them to enlarged cells, followed by squamous metaplasia. In this report, HPV DNA was transfected to adenocarcinoma cells (cultured cell lines) and this showed that HPV causes squamous metaplasia.”
Nakazato – Pathol Int 1997 abstract / PubMed
harleyrider,
Dave isn’t saying that smoking is the only thing which can cause P53 mutations (and I don’t think that you’re saying that HPV is the only thing, either).
What I’m interested in, is how Chris comes up with his 10% of smokers will contract lung cancer. I can’t make those numbers work when I look at actual lung cancer numbers vs. smokers in various populations.
I suspect that it this number comes from extrapolations from relative risk numbers, rather than from the actual incidence rates vs. total smokers in a population.
If there are other factors which also cause similar styles of cancers (eg. HPV), then it is important to at least allow for those numbers in determining what percentage of smokers will likely get lung cancer.
As I said in an earlier thread, a 10% lifetime risk of lung cancer for smokers is significant. However, what if it was actually, say, 3%?
“I suspect that it this number comes from extrapolations from relative risk numbers, rather than from the actual incidence rates vs. total smokers in a population.”
You are nearly right. I first came across the ‘lifetime risk’ analysis in one of Richard Doll’s studies (can’t remember which one – the Doctors’ study I think). He had calculated that the annual death rate from LC in smokers was 166 per 100,000.
So his calculation amounted to:
i) starting with a cohort of 100,000 smokers, 166 assumed to die in year 1 (0.166% or 166/100000).
ii) subtract 166 from the original cohort, so 99,834 survive after 1 year.
iii) 0.166% of these 99,834 die in year 2 = 165.7 (not real people, so no need to be an integer)
iv) subtract the 165.7 from 99,834 leaving 99,668.3 survivors after year 2.
Repeat steps (iii) to (iv) ad nauseam over a presumed lifetime of smoking. This results in the following:
After 40 years, 93,726 smokers survive – hence a 40 year mortality rate of 6.274%
After 50 years there are 92,182 survivors, so 7.818% have died
After 60 years 90,663 survive, 9.337% have died.
And so on. Somewhere in this compound calculation you will reach the figure of 10% of smokers dying from LC – but it is something of a stretch to get there.
The equivalent numbers for LC deaths in non-smokers were 7 per 100,000 per year, which after 60 years results in 0.412% dying from LC (99,588 survivors out of 100,000).
Of course this is all a bit crude. It assumes that all things remain constant over the whole 40 year period, the annual LC death rate, treatment efficacy, smokers continuing to smoke at the same rate etc. – a bit unlikely. It also fails to take account of those who die from other causes during the 40 years.
It’s just a simple form of actuarial analysis, really. But if Doll’s original mortality rates were (hypothetically) double the ‘true’ rate – say it had been only 80 per 100,000 smokers dying each year – then the equivalent 40-year mortality would indeed be just above 3%.
Me? I think 10% (or even 6.274%) instinctively seems too high, but without whole population statistics (impossible since there is no record of every individual’s smoking habits) you have to accept some form of estimate – or not.
You pays your money and you takes your choice.
Brian Bond
This study from Canada reckons the rate is 17.2% of current male smokers and 11.6% of current female smokers will develop lung cancer. (‘Current’ being 1994)
http://www.ncbi.nlm.nih.gov/pubmed/7895211
This stat is the only one cited on Wikipedia’s lung cancer page. I mention that as a point of interest, not as a recommendation.
Chris
I read that study last night too, Chris. It is based on a Canadian sample of study data (meta-analysed IIRC).
Each calculation is only as reliable as the basic assumed mortality rate that you start with. Isn’t that the way of all sample-based (as opposed to population-based) statistics. I just used rates extrapolated from Doll’s samples.
Plus, of course, the mortality rate changes on a year-to-year basis, partly because the initial cohort is being gradually reduced and each new year’s annual mortality rate will be altered by an ever-increasing proportion of folk who started smoking after year 1 of the calculations.
It is really that imprecise. It should be clear that calculating such a lifetime risk will depend on your starting point (which of course determines the assumed ‘current’ mortality rate). Generally if you were to start now, and for a population in which LC incidence has been significantly reducing in recent years, then the lifetime risk will be calculated up to 40/50/60 years in the future, so is most likely to be much smaller than calculations that started (say) 20-30 years back, when mortality rates were generally higher.
In 2009 there were about 30,000 lung cancer deaths in England & Wales (offical ONS statistics). Someone might like to calculate what that means in terms of deaths per 100,000 smokers and compare the predicted lifetime risk from this. Anyone?
I can’t be arsed, to be honest, but my gut feel says it is likely to be slightly higher than Doll’s figures – so probably nearer to the Canadian ones.
Brian Bond
Can’t see any more than the abstract there, unfortunately. Here’s another way of looking at Canada’s lung cancer incidence rates:
http://www.ncic.cancer.ca/Canada-wide/About%20cancer/Cancer%20statistics/Canadian%20Cancer%20Statistics/Special%20topics/Comparison%20of%20cancer%20in%20Canada%20from%201987%20to%201997.aspx?sc_lang=en#ccsfix
In 1987 there were 10721 lung cancer deaths in Canada. Assume that 85% of those are in smokers and ex-smokers, giving 9,113. In 1987, the Canadian population was around 25,500,000:
http://www12.statcan.ca/census-recensement/2006/as-sa/97-550/figures/c2-eng.cfm
Let’s say that 40%, or 10,200,000 are smokers or ex-smokers.
So, we can say that roughly 9,113 of these 10.2m smokers will be diagnosed with lung cancer each year. If we agree that lung cancer doesn’t really happen before 45 years and is mostly finished with by 85 years, then we have a 40 year risk period. So, 9,113 x 40 = 364,520. Then 364,520 ÷ 10.2m = 3.6%
It doesn’t matter where I do this calculation in the Western world, it keeps on coming out at around 3%-4%.
Anon (Gary again?),
The 10% figure is for lifelong smokers. Unless you have data for the number of lifelong smokers you won’t be able to get a fair estimate.
CJS
Lifelong smoker LC proportion
Proportion of lifelong smokers who die of lung cancer:
Using Doll’s 2004 paper on his smoking doctors (1) I estimate the figure at 7% for lifelong cigarette smokers and 5% for pipe/cigar smokers. (This may appear contrary to RR values but I think this is because pipe smokers were older at death).
One problem with this estimate is that many of his study participants were still living and as lung cancer is a disease of old age the 7% figure is probably an underestimate. However I used the same method on his earlier (1994) paper and came up with 6.8% for cigarette smokers, so not much change in ten years.
I took his figures at face value so diagnosis bias would probably make it lower in reality.
Method of estimation:
I used table 1 and looked at the ‘Age standardised mortality rate per 1000 men/year’ for lung cancer and then divided it by the all cause figure. So for current cigarette smokers: 2.49/35.4 = 0.07.
Adjustments etc might make this estimate unreliable so I double checked by using it to calculate actual numbers of deaths for each category. e.g. for current smokers: %age * actual number (as given in table) is 0.07 * 4680 = 329 deaths.
Adding all the categories (smoker, former, non etc) together I estimated 1013 total deaths from lung cancer which compares pretty well with the total given of 1052.
References:
1. http://www.bmj.com/content/328/7455/1519.full.pdf+html?sid=70abdb58-c1f8-497f-a2cb-90c08e73c4f6
Tony
P.S. I also noticed a bizarre anomaly. In his 1994 paper he has 5280 current smoker deaths but by 2004 the number had shrunk to 4680. All other categories increased as you would expect. NB these are actual deaths for the entire cohort, not adjusted ones. So either he has changed the classification retrospectively or at least 600 current smokers came back from the dead!
Benzo(a)pyrene
If Benzo(a)pyrene is present in SHS and Inhaled Smoke why the different effect? If the mechanism is as described, then even non-smokers will be subject to that mechanism, from benzo(a)pyrene, if present in SHS, wouldn’t they? If not why not?
west2
Benzo(a)pyrene
If Benzo(a)pyrene is present in SHS and Inhaled Smoke why the different effect? If the mechanism is as described, then even non-smokers will be subject to that mechanism, from benzo(a)pyrene, if present in SHS, wouldn’t they? If not why not?
west2
Re: Benzo(a)pyrene
The dose maketh the poison.
Re: Benzo(a)pyrene
The dose maketh the poison.
Dave, thank you for being the first person to actually offer something as to why smoking can cause cancer. We’ve been waiting in vain for it for quite some time.
I have some information on p53 which i would like to bring up for your thoughts, but it will have to wait until tomorrow when i get home.
before that though, Dave may i ask a question chris refused to answer: do you believe a cigarette is a cigarette, or that a cigarette is a loose definition for various types i.e. various tpes of tobacco (light, dark, virginia, barley etc), cigarette size in length and width, roll ups vs premade, organic fertiliser vs high phosphate fertiliser and so on?
in other words, do you think all tobacco can cause cancer, or that some tobcco can be problematic just like some foods can be detrimental to health?
Dave, thank you for being the first person to actually offer something as to why smoking can cause cancer. We’ve been waiting in vain for it for quite some time.
I have some information on p53 which i would like to bring up for your thoughts, but it will have to wait until tomorrow when i get home.
before that though, Dave may i ask a question chris refused to answer: do you believe a cigarette is a cigarette, or that a cigarette is a loose definition for various types i.e. various tpes of tobacco (light, dark, virginia, barley etc), cigarette size in length and width, roll ups vs premade, organic fertiliser vs high phosphate fertiliser and so on?
in other words, do you think all tobacco can cause cancer, or that some tobcco can be problematic just like some foods can be detrimental to health?
benzo(a)pyrene
Dave,
I don’t think there is any doubt that benzo(a)pyrene is carcinogenic and I am happy to accept that it causes P53 mutations in sufficient dosage. The trouble is I don’t think the situation is as clear cut as you state. I hope you don’t mind my reposting a note of caution that I originally put on takingliberties:
I noted that the P53 mutations were produced by exposing cells in-vitro (outside the body) to benzo(a)pyrene rather than to tobacco smoke as such .
Apparently small cell lung cancer accounts for around 16% of all lung cancers. Non-small cell lung cancer accounts for 80% of cases.
Which is interesting, considering this evidence from the McTear vs ITL case.
(Professor Idle was an expert witness for ITL):
“[5.542] Under reference to a figure in his report, Professor Idle said that it had been reported that the p53 gene contained mutations in most types of human cancer, ranging from a frequency of between 13% and 14% in prostate carcinoma, up to more than 70% in small cell lung cancer. The frequency in non-small cell lung cancer, which included mainly adenocarcinoma and squamous cell lung cancer, with a frequency of about 40%, placed this group in the middle of the range, so it was no different from other tumours essentially. Professor Idle said that it was noteworthy that, while 40% of non-small cell lung cancer tumours were reported to have had p53 mutations, 60% did not.”
(Richard Doll was an expert witness for McTear):
“[5.302] Finally, Sir Richard was asked about benzo[a]pyrene. He agreed that this substance was produced by everything that was burnt and was present in the air that was breathed. As he had previously said, smoking thirty cigarettes a day was not equivalent to exposure to a strong carcinogen. He had also said that whether cigarette smoke acted even as a weak carcinogen was more difficult to determine, though it was necessary to be careful in the use of these terms, because the quantity of a carcinogen was a factor as well as its strength or weakness: ‘The poison is in the dose.'”
Tony
benzo(a)pyrene
Dave,
I don’t think there is any doubt that benzo(a)pyrene is carcinogenic and I am happy to accept that it causes P53 mutations in sufficient dosage. The trouble is I don’t think the situation is as clear cut as you state. I hope you don’t mind my reposting a note of caution that I originally put on takingliberties:
I noted that the P53 mutations were produced by exposing cells in-vitro (outside the body) to benzo(a)pyrene rather than to tobacco smoke as such .
Apparently small cell lung cancer accounts for around 16% of all lung cancers. Non-small cell lung cancer accounts for 80% of cases.
Which is interesting, considering this evidence from the McTear vs ITL case.
(Professor Idle was an expert witness for ITL):
“[5.542] Under reference to a figure in his report, Professor Idle said that it had been reported that the p53 gene contained mutations in most types of human cancer, ranging from a frequency of between 13% and 14% in prostate carcinoma, up to more than 70% in small cell lung cancer. The frequency in non-small cell lung cancer, which included mainly adenocarcinoma and squamous cell lung cancer, with a frequency of about 40%, placed this group in the middle of the range, so it was no different from other tumours essentially. Professor Idle said that it was noteworthy that, while 40% of non-small cell lung cancer tumours were reported to have had p53 mutations, 60% did not.”
(Richard Doll was an expert witness for McTear):
“[5.302] Finally, Sir Richard was asked about benzo[a]pyrene. He agreed that this substance was produced by everything that was burnt and was present in the air that was breathed. As he had previously said, smoking thirty cigarettes a day was not equivalent to exposure to a strong carcinogen. He had also said that whether cigarette smoke acted even as a weak carcinogen was more difficult to determine, though it was necessary to be careful in the use of these terms, because the quantity of a carcinogen was a factor as well as its strength or weakness: ‘The poison is in the dose.'”
Tony
harleyrider,
Dave isn’t saying that smoking is the only thing which can cause P53 mutations (and I don’t think that you’re saying that HPV is the only thing, either).
What I’m interested in, is how Chris comes up with his 10% of smokers will contract lung cancer. I can’t make those numbers work when I look at actual lung cancer numbers vs. smokers in various populations.
I suspect that it this number comes from extrapolations from relative risk numbers, rather than from the actual incidence rates vs. total smokers in a population.
If there are other factors which also cause similar styles of cancers (eg. HPV), then it is important to at least allow for those numbers in determining what percentage of smokers will likely get lung cancer.
As I said in an earlier thread, a 10% lifetime risk of lung cancer for smokers is significant. However, what if it was actually, say, 3%?
A relevant study:
“Indeed, because dose considerations for known tobacco smoke lung carcinogens account for ≤4% of the lung cancer risk of conventional cigarettes as they are smoked by North American populations, then lowered levels of these toxicants in PREPs still leave PREPs in the possible position of being as harmful as conventional cigarettes. Expressed another way, even if a PREP design were to succeed in removing all currently measured known human lung carcinogens from cigarette smoke (and even perhaps all other currently measured carcinogens), there would be little reason to be confident that such removal would by itself lead to any observable reduction in smoking related lung cancer.”
http://cebp.aacrjournals.org/content/16/3/584.full.pdf+html
A relevant study:
“Indeed, because dose considerations for known tobacco smoke lung carcinogens account for ≤4% of the lung cancer risk of conventional cigarettes as they are smoked by North American populations, then lowered levels of these toxicants in PREPs still leave PREPs in the possible position of being as harmful as conventional cigarettes. Expressed another way, even if a PREP design were to succeed in removing all currently measured known human lung carcinogens from cigarette smoke (and even perhaps all other currently measured carcinogens), there would be little reason to be confident that such removal would by itself lead to any observable reduction in smoking related lung cancer.”
http://cebp.aacrjournals.org/content/16/3/584.full.pdf+html
Another article of interest:
Conclusion:
“Serum levels of vitamin B6 and methionine were inversely associated with risk of lung cancer.”
http://jama.ama-assn.org/content/303/23/2377.abstract
Another article of interest:
Conclusion:
“Serum levels of vitamin B6 and methionine were inversely associated with risk of lung cancer.”
http://jama.ama-assn.org/content/303/23/2377.abstract
somewhat consistent with…
http://cebp.aacrjournals.org/content/15/8/1526.abstract
A Phase I Study of myo-Inositol for Lung Cancer Chemoprevention
Results: The maximum tolerated dose was found to be 18 g/d. Side effects, when present, were mild and mainly gastrointestinal in nature. Using the regression rate of the placebo subjects from a recently completed clinical trial with the same inclusion/exclusion criteria as a comparison, a significant increase in the rate of regression of preexisting dysplastic lesions was observed (91% versus 48%; P = 0.014). A statistically significant reduction in the systolic and diastolic blood pressures by an average of 10 mm Hg was observed after taking 18 g/d of myo-inositol for a month or more.
*****
From wiki — just to clarify
Myo-Inositol was once classified as a member of the vitamin B complex.[citation needed] However, because it is produced by the human body from glucose, it is not an essential nutrient. Some substances such as niacin can also be synthesized in the body, but are not made in amounts considered adequate for good health, and thus are still classified as essential nutrients. However, there is no convincing evidence that this is the case for myo-inositol.
In a number of posts people have pointed out the factor of diet; I have mentioned biological variation.
Firstly – it should not be too difficult to find foods containing an ample amount/day intake of this vitamin.
http://www.weightlossforall.com/foods-rich-vitamin-b6.htm
Secondly – looking at the numerous processes this vitamin is involved in.
(good old Wikipedia)
http://en.wikipedia.org/wiki/Vitamin_B6
looking at the various processes affected by this vitamin + the numerous knock on effects on other processes leads to the question can there really by only ONE MALFUNCTION for the genesis and manifestation of any given type of cancer?
Just to add to the discussion —
Dave said
“The inhalation of benzo(a)pyrene causes a guanine to thymine transversion where within the DNA of the p53 gene the guanine and tymine molecules change position within the helix of the DNA rendering the p53 inert and the onco (cancer) gene K ras allows the cancer cells to develop. That medically and scientifically is the reason that smoking directly causes lung cancer.”
As I understand the issue, marijuana smoke contains much higher levels of benzopyrene (vs tobacco smoke), is inhaled more deeply, yet appears to be protective against lung and neck cancers.
http://www.washingtonpost.com/wp-dyn/content/article/2006/05/25/AR2006052501729.html
“The largest study of its kind has unexpectedly concluded that smoking marijuana, even regularly and heavily, does not lead to lung cancer.
The new findings “were against our expectations,” said Donald Tashkin of the University of California at Los Angeles, a pulmonologist who has studied marijuana for 30 years.
“We hypothesized that there would be a positive association between marijuana use and lung cancer, and that the association would be more positive with heavier use,” he said. “What we found instead was no association at all, and even a suggestion of some protective effect.”
Federal health and drug enforcement officials have widely used Tashkin’s previous work on marijuana to make the case that the drug is dangerous. Tashkin said that while he still believes marijuana is potentially harmful, its cancer-causing effects appear to be of less concern than previously thought.
Earlier work established that marijuana does contain cancer-causing chemicals as potentially harmful as those in tobacco, he said. However, marijuana also contains the chemical THC, which he said may kill aging cells and keep them from becoming cancerous….”
As I understand it, benzopyrene by itself is pretty good at inducing cancer in animals, tobacco smoke just makes them live longer.
Just to add to the discussion —
Dave said
“The inhalation of benzo(a)pyrene causes a guanine to thymine transversion where within the DNA of the p53 gene the guanine and tymine molecules change position within the helix of the DNA rendering the p53 inert and the onco (cancer) gene K ras allows the cancer cells to develop. That medically and scientifically is the reason that smoking directly causes lung cancer.”
As I understand the issue, marijuana smoke contains much higher levels of benzopyrene (vs tobacco smoke), is inhaled more deeply, yet appears to be protective against lung and neck cancers.
http://www.washingtonpost.com/wp-dyn/content/article/2006/05/25/AR2006052501729.html
“The largest study of its kind has unexpectedly concluded that smoking marijuana, even regularly and heavily, does not lead to lung cancer.
The new findings “were against our expectations,” said Donald Tashkin of the University of California at Los Angeles, a pulmonologist who has studied marijuana for 30 years.
“We hypothesized that there would be a positive association between marijuana use and lung cancer, and that the association would be more positive with heavier use,” he said. “What we found instead was no association at all, and even a suggestion of some protective effect.”
Federal health and drug enforcement officials have widely used Tashkin’s previous work on marijuana to make the case that the drug is dangerous. Tashkin said that while he still believes marijuana is potentially harmful, its cancer-causing effects appear to be of less concern than previously thought.
Earlier work established that marijuana does contain cancer-causing chemicals as potentially harmful as those in tobacco, he said. However, marijuana also contains the chemical THC, which he said may kill aging cells and keep them from becoming cancerous….”
As I understand it, benzopyrene by itself is pretty good at inducing cancer in animals, tobacco smoke just makes them live longer.
“I suspect that it this number comes from extrapolations from relative risk numbers, rather than from the actual incidence rates vs. total smokers in a population.”
You are nearly right. I first came across the ‘lifetime risk’ analysis in one of Richard Doll’s studies (can’t remember which one – the Doctors’ study I think). He had calculated that the annual death rate from LC in smokers was 166 per 100,000.
So his calculation amounted to:
i) starting with a cohort of 100,000 smokers, 166 assumed to die in year 1 (0.166% or 166/100000).
ii) subtract 166 from the original cohort, so 99,834 survive after 1 year.
iii) 0.166% of these 99,834 die in year 2 = 165.7 (not real people, so no need to be an integer)
iv) subtract the 165.7 from 99,834 leaving 99,668.3 survivors after year 2.
Repeat steps (iii) to (iv) ad nauseam over a presumed lifetime of smoking. This results in the following:
After 40 years, 93,726 smokers survive – hence a 40 year mortality rate of 6.274%
After 50 years there are 92,182 survivors, so 7.818% have died
After 60 years 90,663 survive, 9.337% have died.
And so on. Somewhere in this compound calculation you will reach the figure of 10% of smokers dying from LC – but it is something of a stretch to get there.
The equivalent numbers for LC deaths in non-smokers were 7 per 100,000 per year, which after 60 years results in 0.412% dying from LC (99,588 survivors out of 100,000).
Of course this is all a bit crude. It assumes that all things remain constant over the whole 40 year period, the annual LC death rate, treatment efficacy, smokers continuing to smoke at the same rate etc. – a bit unlikely. It also fails to take account of those who die from other causes during the 40 years.
It’s just a simple form of actuarial analysis, really. But if Doll’s original mortality rates were (hypothetically) double the ‘true’ rate – say it had been only 80 per 100,000 smokers dying each year – then the equivalent 40-year mortality would indeed be just above 3%.
Me? I think 10% (or even 6.274%) instinctively seems too high, but without whole population statistics (impossible since there is no record of every individual’s smoking habits) you have to accept some form of estimate – or not.
You pays your money and you takes your choice.
Brian Bond
Catch 15
Hello Dave.
At last we have an answer! The reason that Smoking causes lung cancer is Benzo-pyrene. At last! The matter is now settled! Benzo-pyrene causes a mutation in the p53 gene (guanine/thymine transposition) so that the p53 gene ceases to do its job of ‘eliminating’ or ‘blocking’ cancer cells. When that happens the K ras gene is allowed (?) to allow cancer cells to develop. Benzo p is THE CAUSE of lung cancer in smokers. QED. Or is it?
Prof Helland said that the K ras gene MUTATES. Dave, you did not say that the K ras gene mutates! You said that the p53 gene mutates. You see? We have a little confusion already.
But Prof Helland goes on: The K ras gene is OFTEN mutated in smoker’s tumours but SELDOM in the tumours of non-smokers. Often? Seldom? How often? How seldom? He implies that sometimes the K ras gene is NOT mutated in the tumours of smokers and sometimes the K ras gene IS mutated in non-smokers. So, if the K ras gene is sometimes NOT mutated in the tumours of smokers, why do these smokers have lung cancer?
But he goes on: the EFGR gene is NOT mutated in smokers. Why not? If it is mutated in non-smokers, then it must be some sort of general mutation which applies to everyone. Why does it not occur in smokers? Could it be that smoking cigarettes provides protection from this mutation? (But note that he does not say that the EFGR gene is mutated in ALL non-smokers’ tumours! – just that it is mutated in the tumours on non-smokers).
But then, in the last sentence, Dave introduces the p24 gene, which has not figured before. In this sentence, Dave introduces three classes: Smokers, ex-smokers and non-smokers.
Now then. Just let me think.
Smokers continue to damage the p53 gene. They do not develop galloping lung cancer because……..erm……….don’t know. Non-smokers have something or other stabilized. What has been stabilized and why do they need to have anything stabilized when they are non-smokers and have not been damaging their p53 gene? As regards ex-smokers, they have not continued to damage the p53 gene nor has whatever stabilized, but the p24 gene does not do something, and so they get galloping lung cancer!
Nothing in the last sentence makes any sense whatsoever! Is it any wonder that we have the Surgeon general of the USA claiming that the slightest whiff of cigarette smoke can cause a perfectly healthy person to have a heart attack?
In conclusion, it seems to me that every time we get close to an answer to the question with which we started, the answer turns out to be just another load of uncertainties.
And so, at the end of the day, we come back to the assertion that it does not matter to me, as an adult, free Englishman whether smoking causes lung cancer or not. The fact of the matter is that I simply enjoy it, just as I enjoy beer, wine, cream cakes and chocolate – and, there are those who enjoy climbing mountains, regardless of the risk. Children? That must surely be the responsibility of their parents – in any case, there is no evidence whatsoever that children are affected in any way at all.
Catch 15
Hello Dave.
At last we have an answer! The reason that Smoking causes lung cancer is Benzo-pyrene. At last! The matter is now settled! Benzo-pyrene causes a mutation in the p53 gene (guanine/thymine transposition) so that the p53 gene ceases to do its job of ‘eliminating’ or ‘blocking’ cancer cells. When that happens the K ras gene is allowed (?) to allow cancer cells to develop. Benzo p is THE CAUSE of lung cancer in smokers. QED. Or is it?
Prof Helland said that the K ras gene MUTATES. Dave, you did not say that the K ras gene mutates! You said that the p53 gene mutates. You see? We have a little confusion already.
But Prof Helland goes on: The K ras gene is OFTEN mutated in smoker’s tumours but SELDOM in the tumours of non-smokers. Often? Seldom? How often? How seldom? He implies that sometimes the K ras gene is NOT mutated in the tumours of smokers and sometimes the K ras gene IS mutated in non-smokers. So, if the K ras gene is sometimes NOT mutated in the tumours of smokers, why do these smokers have lung cancer?
But he goes on: the EFGR gene is NOT mutated in smokers. Why not? If it is mutated in non-smokers, then it must be some sort of general mutation which applies to everyone. Why does it not occur in smokers? Could it be that smoking cigarettes provides protection from this mutation? (But note that he does not say that the EFGR gene is mutated in ALL non-smokers’ tumours! – just that it is mutated in the tumours on non-smokers).
But then, in the last sentence, Dave introduces the p24 gene, which has not figured before. In this sentence, Dave introduces three classes: Smokers, ex-smokers and non-smokers.
Now then. Just let me think.
Smokers continue to damage the p53 gene. They do not develop galloping lung cancer because……..erm……….don’t know. Non-smokers have something or other stabilized. What has been stabilized and why do they need to have anything stabilized when they are non-smokers and have not been damaging their p53 gene? As regards ex-smokers, they have not continued to damage the p53 gene nor has whatever stabilized, but the p24 gene does not do something, and so they get galloping lung cancer!
Nothing in the last sentence makes any sense whatsoever! Is it any wonder that we have the Surgeon general of the USA claiming that the slightest whiff of cigarette smoke can cause a perfectly healthy person to have a heart attack?
In conclusion, it seems to me that every time we get close to an answer to the question with which we started, the answer turns out to be just another load of uncertainties.
And so, at the end of the day, we come back to the assertion that it does not matter to me, as an adult, free Englishman whether smoking causes lung cancer or not. The fact of the matter is that I simply enjoy it, just as I enjoy beer, wine, cream cakes and chocolate – and, there are those who enjoy climbing mountains, regardless of the risk. Children? That must surely be the responsibility of their parents – in any case, there is no evidence whatsoever that children are affected in any way at all.
The last was from Junican. I do not understand why the machine allowed me to post it!
The last was from Junican. I do not understand why the machine allowed me to post it!
Okay, now I am really confused.
“The reason why ex smokers are at risk and have much higher rates of lung cancer is that once a gene is mutated the p24 gene is unable to repair the DNA damage. While smokers continue to damage their p53 gene by continually smoking the damage with non smokers stabilises. ”
What does this mean?
Does this mean if someone smokes – and continues to smoke – then they are less apt to get lung cancer than someone who smokes, but because of nannying, bullying, taxation, bans and general discrimination caves into ASH and the do-gooders and quits smoking – then that person will now become highly susceptible to having lung cancer?
And if so – then if someone stops smoking – in order to stave off getting lung cancer – is it wiser for that person to begin taking up smoking again – and soon? Is there a time period over which once you stop smoking, if you do not start back up, then you are dooming yourself for a super increased rate of lung cancer?
If this is the case and what you are saying – then aren’t all these people going around trying to bully everyone into stopping smoking actually trying to harm and kill all these people, that their efforts to get people to stop are just going to make matters worse instead of better?
And isn’t that just cruel, especially given the fact that SHS isn’t harmful in the first place to all these do-gooders demanding everyone else in society stop?
That seems seriously wrong, if people are being asked to stop smoking in order to increase their susceptibility to lung cancer, when if just left alone, the smokers’ rates as well as the non-smokers’ rates would have remained stable. The way it is, it sounds like they are sounding a death bell for all smokers by forcing them to not smoke.
Okay, now I am really confused.
“The reason why ex smokers are at risk and have much higher rates of lung cancer is that once a gene is mutated the p24 gene is unable to repair the DNA damage. While smokers continue to damage their p53 gene by continually smoking the damage with non smokers stabilises. ”
What does this mean?
Does this mean if someone smokes – and continues to smoke – then they are less apt to get lung cancer than someone who smokes, but because of nannying, bullying, taxation, bans and general discrimination caves into ASH and the do-gooders and quits smoking – then that person will now become highly susceptible to having lung cancer?
And if so – then if someone stops smoking – in order to stave off getting lung cancer – is it wiser for that person to begin taking up smoking again – and soon? Is there a time period over which once you stop smoking, if you do not start back up, then you are dooming yourself for a super increased rate of lung cancer?
If this is the case and what you are saying – then aren’t all these people going around trying to bully everyone into stopping smoking actually trying to harm and kill all these people, that their efforts to get people to stop are just going to make matters worse instead of better?
And isn’t that just cruel, especially given the fact that SHS isn’t harmful in the first place to all these do-gooders demanding everyone else in society stop?
That seems seriously wrong, if people are being asked to stop smoking in order to increase their susceptibility to lung cancer, when if just left alone, the smokers’ rates as well as the non-smokers’ rates would have remained stable. The way it is, it sounds like they are sounding a death bell for all smokers by forcing them to not smoke.
I think maybe we should take a look at the fact that since the junk shs propaganda people are questioning all the science now!
It could very well be we are witnessing a real change in the future of public health and those who push it as the populace braves to say,your full of shit and we dont believe anything else you may have to say!
I see this as the near future,Why else would 70-80 years ago those same prohibitionists create the ACS,ALA,AHA and so many other supposed non-profit orginizations at the end of the last prohibition movement.Was it to gain a new trusted face after our grand parents quit believeing them same anti-tobacco,anti alcohol pushers of that time……It will end the same way it did last time,but what dark corner of society will they hide in next,just to raise their hatred and eugenics against us all again……could that be the reason warren buffet and bloomberg,gates and so many others are trying to get philantropy well funded as this past one collapses from its own demise and public dislike for what they have become…
I say we are seeing history repeat itself again as the end comes full circle for the nanny staters and their new attempt at an old enemy prohibition!
I think maybe we should take a look at the fact that since the junk shs propaganda people are questioning all the science now!
It could very well be we are witnessing a real change in the future of public health and those who push it as the populace braves to say,your full of shit and we dont believe anything else you may have to say!
I see this as the near future,Why else would 70-80 years ago those same prohibitionists create the ACS,ALA,AHA and so many other supposed non-profit orginizations at the end of the last prohibition movement.Was it to gain a new trusted face after our grand parents quit believeing them same anti-tobacco,anti alcohol pushers of that time……It will end the same way it did last time,but what dark corner of society will they hide in next,just to raise their hatred and eugenics against us all again……could that be the reason warren buffet and bloomberg,gates and so many others are trying to get philantropy well funded as this past one collapses from its own demise and public dislike for what they have become…
I say we are seeing history repeat itself again as the end comes full circle for the nanny staters and their new attempt at an old enemy prohibition!
@(Anonymous)2010-12-15 05:37 am (UTC)
I don’t think Dave was saying that.. but I do think you have expressed a truth. Older research on smoking cessation easily shows ex-smokers having lower LC rates than current smokers – back in the day when people gave up smoking voluntarily. More recent research is less likely to demonstrate significant “risk” reduction – and may even indicate increases in “risk” for former smokers (like MRFIT). This seems consistent with a medicinal effect of smoking. It could be compared to making asthmatics give up their inhalers. The first wave, those who give them up voluntarily aren’t likely to have many more asthma attacks than the general population (non-inhaler users). However, later waves, those who have the inhalers ripped from their hands (probably based on the theory that there is such a strong association between inhaler use and asthma that therefore inhalers must CAUSE asthma) — will find themselves at higher risk of attacks than never users OR continuing users.
@(Anonymous)2010-12-15 05:37 am (UTC)
I don’t think Dave was saying that.. but I do think you have expressed a truth. Older research on smoking cessation easily shows ex-smokers having lower LC rates than current smokers – back in the day when people gave up smoking voluntarily. More recent research is less likely to demonstrate significant “risk” reduction – and may even indicate increases in “risk” for former smokers (like MRFIT). This seems consistent with a medicinal effect of smoking. It could be compared to making asthmatics give up their inhalers. The first wave, those who give them up voluntarily aren’t likely to have many more asthma attacks than the general population (non-inhaler users). However, later waves, those who have the inhalers ripped from their hands (probably based on the theory that there is such a strong association between inhaler use and asthma that therefore inhalers must CAUSE asthma) — will find themselves at higher risk of attacks than never users OR continuing users.
“The basic scientific reason for lung cancer in active smokers is genetic mutation caused by smoking. All us have on chromosome 17 the tumor protein gene 53 or p53. Its function “p53 is important in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer. As such, p53 has been described as “the guardian of the genome”, the “guardian angel gene”, and the “master watchman”, referring to its role in conserving stability by preventing genome mutation. ” Putting it simply it stops cancer cells dividing.”
To keep it simple; p53 is involved in the induction of apoptosis as well as the DNA repair mechanism.
Perhaps we should also look much closer into what is involved in DNA repair.
“Damage to our genetic material is an ongoing threat to both our ability to faithfully transmit genetic information to our offspring as well as our own survival. To respond to these threats, eukaryotes have evolved the DNA damage response (DDR). The DDR is a complex signal transduction pathway that has the ability to sense DNA damage and transduce this information to the cell to influence cellular responses to DNA damage. Cells possess an arsenal of enzymatic tools capable of remodeling and repairing DNA; however, their activities must be tightly regulated in a temporal, spatial, and DNA lesion-appropriate fashion to optimize repair and prevent unnecessary and potentially deleterious alterations in the structure of DNA during normal cellular processes. This review will focus on how the DDR controls DNA repair and the phenotypic consequences of defects in these critical regulatory functions in mammals.”
Regulation of DNA repair mechanism:
http://www.evolutionnews.org/2010/11/regulating_dna_repair_mechanis040801.html
http://www.ncbi.nlm.nih.gov/books/NBK13516/
I personally believe that active smoking might be just one of numerous factors which can play a role in carcinogenesis.
SHS is a completely different matter.
“The basic scientific reason for lung cancer in active smokers is genetic mutation caused by smoking. All us have on chromosome 17 the tumor protein gene 53 or p53. Its function “p53 is important in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer. As such, p53 has been described as “the guardian of the genome”, the “guardian angel gene”, and the “master watchman”, referring to its role in conserving stability by preventing genome mutation. ” Putting it simply it stops cancer cells dividing.”
To keep it simple; p53 is involved in the induction of apoptosis as well as the DNA repair mechanism.
Perhaps we should also look much closer into what is involved in DNA repair.
“Damage to our genetic material is an ongoing threat to both our ability to faithfully transmit genetic information to our offspring as well as our own survival. To respond to these threats, eukaryotes have evolved the DNA damage response (DDR). The DDR is a complex signal transduction pathway that has the ability to sense DNA damage and transduce this information to the cell to influence cellular responses to DNA damage. Cells possess an arsenal of enzymatic tools capable of remodeling and repairing DNA; however, their activities must be tightly regulated in a temporal, spatial, and DNA lesion-appropriate fashion to optimize repair and prevent unnecessary and potentially deleterious alterations in the structure of DNA during normal cellular processes. This review will focus on how the DDR controls DNA repair and the phenotypic consequences of defects in these critical regulatory functions in mammals.”
Regulation of DNA repair mechanism:
http://www.evolutionnews.org/2010/11/regulating_dna_repair_mechanis040801.html
http://www.ncbi.nlm.nih.gov/books/NBK13516/
I personally believe that active smoking might be just one of numerous factors which can play a role in carcinogenesis.
SHS is a completely different matter.
A few quick responses
@Harley Rider
Just a few quick responses, I’ll try and be more detailed later.
HPV 16 and 18 (genital warts to you and me)have been suggested as one of the causes of lung cancer in non smokers. HPV is the SOLE reason for cervical cancer. The RR for smoking is 2.72 and the CI intevals are off the top of my head 1.5-3.8, statistically significant. Now we know that the correlation is that promiscuous people tend to contract HPV and promiscuous people tend to smoke by a factor of 2.72.
G to T transversions are not unique to smoking but these mutations on smokers are clustered around the the upper reaches of the lung.
http://lungcancer.about.com/od/causesoflungcance1/f/hpvlungcancer.htm
A few quick responses
@Harley Rider
Just a few quick responses, I’ll try and be more detailed later.
HPV 16 and 18 (genital warts to you and me)have been suggested as one of the causes of lung cancer in non smokers. HPV is the SOLE reason for cervical cancer. The RR for smoking is 2.72 and the CI intevals are off the top of my head 1.5-3.8, statistically significant. Now we know that the correlation is that promiscuous people tend to contract HPV and promiscuous people tend to smoke by a factor of 2.72.
G to T transversions are not unique to smoking but these mutations on smokers are clustered around the the upper reaches of the lung.
http://lungcancer.about.com/od/causesoflungcance1/f/hpvlungcancer.htm
With a certain amount of trepidation, I will post this for Dave again.
Last time he told me to visit a doctor if I thought I was sick.
Which was something of a surprise.
It’s the mechanism by which the p53 appears to be protected.
Inhaling
“The fact, however, and it is a fact that should have interested Hill and Doll in 1950, is that inhalers get fewer cancers. and the difference is statistically significant”
“The failure of Hill and Doll’s retrospective inquiry to supply such corroboration took these workers by surprise, and at first they could
scarcely believe the question had been understood.
The investigators who actually questioned the patients, however, seem to have had no doubt of this; and the statisticians had the embarrassing choice between frankly avowing that one striking and unexpected result of their enquiry was clearly contrary to the expectations of the theory they advanced, or to take the timid and unsatisfactory course of saying as little about it as possible.”
Click to access fisher276a.pdf
Seek, and ye shall find.
Mapping the role of NAD metabolism in prevention and treatment of carcinogenesis
“Studies presented here show that cellular NAD, which we hypothesize to be the relevant biomarker of niacin status, is significantly lower in humans than in the commonly studied animal models of carcinogenesis.
We show that nicotinamide and the resulting cellular NAD concentration modulate expression of the tumor suppressor protein, p53, in human breast, skin, and lung cells.
Studies to determine the optimal NAD concentrations for responding to DNA damage in breast epithelial cells reveal that DNA damage appears to stimulate NAD biosynthesis and that recovery from DNA damage occurs several hours earlier in the presence of higher NAD or in cells undergoing active NAD biosynthesis.
Finally, analyses of normal human skin tissue from individuals diagnosed with actinic keratoses or squamous cell carcinomas show that NAD content of the skin is inversely correlated with the malignant phenotype. Since NAD is important in modulating ADP-ribose polymer metabolism, cyclic ADP-ribose synthesis, and stress response proteins, such as p53, following DNA damage, understanding how NAD metabolism is regulated in the human has important implications in developing both prevention and treatment strategies in carcinogenesis”
“The association of lower NAD with malignancy in skin supports the hypothesis that niacin maybe an important preventive factor in cancer.”
Click to access MappingroleofNADmetabolism.pdf
NIACIN AND NIACINAMIDE IN FLUE-CURED CIGARETTE SMOKE CONDENSATE
http://legacy.library.ucsf.edu/action/document/page?tid=pnx69d00&page=1
Nicotinic Acid Content of Old Gold smoke. – 1941
http://tobaccodocuments.org/product_design/04365497-5498.html
Many other studies which basically say same thing, including by topical application, available on request.
Rose
With a certain amount of trepidation, I will post this for Dave again.
Last time he told me to visit a doctor if I thought I was sick.
Which was something of a surprise.
It’s the mechanism by which the p53 appears to be protected.
Inhaling
“The fact, however, and it is a fact that should have interested Hill and Doll in 1950, is that inhalers get fewer cancers. and the difference is statistically significant”
“The failure of Hill and Doll’s retrospective inquiry to supply such corroboration took these workers by surprise, and at first they could
scarcely believe the question had been understood.
The investigators who actually questioned the patients, however, seem to have had no doubt of this; and the statisticians had the embarrassing choice between frankly avowing that one striking and unexpected result of their enquiry was clearly contrary to the expectations of the theory they advanced, or to take the timid and unsatisfactory course of saying as little about it as possible.”
Click to access fisher276a.pdf
Seek, and ye shall find.
Mapping the role of NAD metabolism in prevention and treatment of carcinogenesis
“Studies presented here show that cellular NAD, which we hypothesize to be the relevant biomarker of niacin status, is significantly lower in humans than in the commonly studied animal models of carcinogenesis.
We show that nicotinamide and the resulting cellular NAD concentration modulate expression of the tumor suppressor protein, p53, in human breast, skin, and lung cells.
Studies to determine the optimal NAD concentrations for responding to DNA damage in breast epithelial cells reveal that DNA damage appears to stimulate NAD biosynthesis and that recovery from DNA damage occurs several hours earlier in the presence of higher NAD or in cells undergoing active NAD biosynthesis.
Finally, analyses of normal human skin tissue from individuals diagnosed with actinic keratoses or squamous cell carcinomas show that NAD content of the skin is inversely correlated with the malignant phenotype. Since NAD is important in modulating ADP-ribose polymer metabolism, cyclic ADP-ribose synthesis, and stress response proteins, such as p53, following DNA damage, understanding how NAD metabolism is regulated in the human has important implications in developing both prevention and treatment strategies in carcinogenesis”
“The association of lower NAD with malignancy in skin supports the hypothesis that niacin maybe an important preventive factor in cancer.”
Click to access MappingroleofNADmetabolism.pdf
NIACIN AND NIACINAMIDE IN FLUE-CURED CIGARETTE SMOKE CONDENSATE
http://legacy.library.ucsf.edu/action/document/page?tid=pnx69d00&page=1
Nicotinic Acid Content of Old Gold smoke. – 1941
http://tobaccodocuments.org/product_design/04365497-5498.html
Many other studies which basically say same thing, including by topical application, available on request.
Rose
This study from Canada reckons the rate is 17.2% of current male smokers and 11.6% of current female smokers will develop lung cancer. (‘Current’ being 1994)
http://www.ncbi.nlm.nih.gov/pubmed/7895211
This stat is the only one cited on Wikipedia’s lung cancer page. I mention that as a point of interest, not as a recommendation.
This is an interesting thread, and I’m surprised Chris didn’t mention P53 when i said no biological evidence exists for smoking causing cancer.
In light of everything that’s been posted on here, i’m not sure i have anything else of value to add. However, there are some questions and points:
Firstly, if we really have a ’cause and effect’, why is the effect not much higher e.g. 70% of smokers getting LC rather than 10% (or less as Brian Bond explained)? You wouldn’t put a match to paper and only have it catch alight 10% of the time.
Secondly, as a development from the first, could it be that the damage is caused by certain brands or tobacco types? If the BAP caused it, then surely the answer is ‘no’, because BAP is present in every brand, every form of smoke and the air we breathe.
Third, is there p53 damage to non-smokers, or only smokers? The problem with this debate is that we will always be able to say, as Lord Nimmo in the McTear case said, ‘yeah but we don’t know if the cancer would have occured had they been a non-smoker’.
Now, my own observations on p53 from my book. The 1996 paper that started all this fuss said:
“Cigarette smoke carcinogens such as benzo[a]pyrene are implicated in the development of lung cancer. The distribution of benzo[a]pyrene diol epoxide (BPDE) adducts along exons of the P53 gene in BPDE-treated HeLa cells and bronchial epithelial cells was mapped at nucleotide resolution. Strong and selective adduct formation occurred at guanine positions in codons 157, 248, and 273. These same positions are the major mutational hotspots in human lung cancers. Thus, targeted adduct formation rather than phenotypic selection appears to shape the P53 mutational spectrum in lung cancer. These results provide a direct etiological link between a defined chemical carcinogen and human cancer.”
BAP is a possible human carcinogen, not a known one, and the richest source of it is leafy vegetables, where they pick it up from the air. Next, like the tobacco ‘condensate’, the researchers didn’t use tobacco smoke but an isolated compound, which is very different to smoke itself. In nutrition, eating select foods together can increase or decrease nutritional potency, it’s just biochemistry; with smoke, removing something isolated doesn’t account for any effect the other compounds have on it.
Next, in this study, 60% of the cancers had the p53 mutation, which means that almost half of the cases had no mutation – the gene apparently has no effect on the onset of the disease then.
Also, I wrote in my book, “the researchers did not actually study any human lung cancers. Instead of human lung cancers, they looked at cultured human cells which they exposed to a “metabolite” of BAP, known as Benzo[a]pyrene diolepoxide (BAPDE). The researchers then tested the cells for mutational damage and said they found mutations at certain locations on the genes, similar to those in 60% of lung cancer cases…They claimed that the mutations were similar to those in 60% of lung cancer cases, but they did not say identical. It would be interesting to see in what regard they were similar, as that could mean anything from size to location.”
Basically then, in this study, human lungs weren’t used, BAP wasn’t used, 60% showed similarities to human lung cases so almost half didn’t. The researchers also say BAP needs to be converted to BAPDE to be a carcinogen, so we need to find out if the lungs can cause this transformation or not. Lastly, there was no comparison made between smokers and non-smokers lungs either.
This is an interesting thread, and I’m surprised Chris didn’t mention P53 when i said no biological evidence exists for smoking causing cancer.
In light of everything that’s been posted on here, i’m not sure i have anything else of value to add. However, there are some questions and points:
Firstly, if we really have a ’cause and effect’, why is the effect not much higher e.g. 70% of smokers getting LC rather than 10% (or less as Brian Bond explained)? You wouldn’t put a match to paper and only have it catch alight 10% of the time.
Secondly, as a development from the first, could it be that the damage is caused by certain brands or tobacco types? If the BAP caused it, then surely the answer is ‘no’, because BAP is present in every brand, every form of smoke and the air we breathe.
Third, is there p53 damage to non-smokers, or only smokers? The problem with this debate is that we will always be able to say, as Lord Nimmo in the McTear case said, ‘yeah but we don’t know if the cancer would have occured had they been a non-smoker’.
Now, my own observations on p53 from my book. The 1996 paper that started all this fuss said:
“Cigarette smoke carcinogens such as benzo[a]pyrene are implicated in the development of lung cancer. The distribution of benzo[a]pyrene diol epoxide (BPDE) adducts along exons of the P53 gene in BPDE-treated HeLa cells and bronchial epithelial cells was mapped at nucleotide resolution. Strong and selective adduct formation occurred at guanine positions in codons 157, 248, and 273. These same positions are the major mutational hotspots in human lung cancers. Thus, targeted adduct formation rather than phenotypic selection appears to shape the P53 mutational spectrum in lung cancer. These results provide a direct etiological link between a defined chemical carcinogen and human cancer.”
BAP is a possible human carcinogen, not a known one, and the richest source of it is leafy vegetables, where they pick it up from the air. Next, like the tobacco ‘condensate’, the researchers didn’t use tobacco smoke but an isolated compound, which is very different to smoke itself. In nutrition, eating select foods together can increase or decrease nutritional potency, it’s just biochemistry; with smoke, removing something isolated doesn’t account for any effect the other compounds have on it.
Next, in this study, 60% of the cancers had the p53 mutation, which means that almost half of the cases had no mutation – the gene apparently has no effect on the onset of the disease then.
Also, I wrote in my book, “the researchers did not actually study any human lung cancers. Instead of human lung cancers, they looked at cultured human cells which they exposed to a “metabolite” of BAP, known as Benzo[a]pyrene diolepoxide (BAPDE). The researchers then tested the cells for mutational damage and said they found mutations at certain locations on the genes, similar to those in 60% of lung cancer cases…They claimed that the mutations were similar to those in 60% of lung cancer cases, but they did not say identical. It would be interesting to see in what regard they were similar, as that could mean anything from size to location.”
Basically then, in this study, human lungs weren’t used, BAP wasn’t used, 60% showed similarities to human lung cases so almost half didn’t. The researchers also say BAP needs to be converted to BAPDE to be a carcinogen, so we need to find out if the lungs can cause this transformation or not. Lastly, there was no comparison made between smokers and non-smokers lungs either.
“The dose maketh the poison.”
1957
“Dr. E. L, Wynder of Sloan-Kettering Institute, a leading proponent of the cigarette theory of lung cancer, reported only this year that:
“The benzpyrene content of tobacco tar is not more than 2 parts per million which, according to our experiments, is not sufficient to produce the type of activity noted in our animals painted with tobacco tar.”
The substance frequently is produced in minute quantities in the burning of any organic compound and is present in varying degrees in city air.
Recent reports in England show that the daily intake of benzpyrene from breathing London air is equivalent in total volume to the intake from smoking about 100 cigarettes a day.”
http://tobaccodocuments.org/ctr/CTRMN043191-3193.html
Testimony of Dr Hueper 1957
“They manipulated the evidence. Anyone who introduces a corrective factor in his calculations to make the evidence fit a preconceived idea, I do not feel that this is valid scientific evidence.
“Do you feel, in view of what you said, that the application of a corrective factor means a predetermined manipulation in this case?
A.In this case I could not say, no.
Q I want to get clear on that.You asked me to read on. I will do that. This appears on Page 435 of your May, 1957 article and reads;
“However, even this estimate is heavily biased by the arbitrary assumption that the benzpyrene content present allegedly in cigarette smoke was about 12 times as effective in eliciting cancers as benzpyrene demonstrated in atmospheric air.
Only when such a “corrective” coefficient is applied was it possible to obtain proportional correlations between the total exposure to benzpyrene from both cigarette smoking and air pollutants and the relative incidence rates of lung cancer found in the industrialized metropolitan Liverpool area, an intermediary urban-rural region, and the rural area of North Wales”
A That is right.
Q That was your statement.
A I would like to have that on the record too.
Q All right. It is in Doctor”
http://tobaccodocuments.org/rjr/503243231-3367.html?zoom=750&ocr_position=above_foramatted&start_page=91
I’m not sure if this has been posted.
Auerbach’s Smoking Beagles [Discusses Response of A Dog to An Inhalation Experiment States That These Methods Produced A Carcinoma in the Animal]
“One dog, which was an inveterate smoker [?], was placed in a stall to demonstrate how the animal smoked.
We used a University Kentucky reference cigarette.
The dog’s handler, Mr. David Kirman, recognized the cigarette to be stronger than the brand they were using, and the behavior of the dog showed that he too was not used to this kind ofsmoke.
The lighting puff was not given to the dog but was made by the pump attached to the cigarette holder.
Thereafter the dog did its own smoking.
Counting the puff that the dog took and also looking at the records, it was obvious that the animal took between 20 to 30 shallow ones per cigarette.
The amount of smoke could be regulated by the attendant by pinching of the tube leading from the cigarette to the tracheostomy tube.
During the demonstration Mr Kirman did this when the dog became cyanotic,very restless, and salivated excessively.
During the smoking period which last 8-10 minutes, smoke poured out of the dog’s mouth and nose.
There were moments when the animal was in obvious distress.
Mr Kirman states that there are 40 dogs still smoking and that the tests will continue.”
http://tobaccodocuments.org/ctr/CTRMN043263-3264.html
Chilling.
Rose
Chilling indeed.
“Recent reports in England show that the daily intake of benzpyrene from breathing London air is equivalent in total volume to the intake from smoking about 100 cigarettes a day.””
Wonderful! Perfectly illustrates my point much earlier on about the components of tobacco smoke being the same as everyday air but in lower dosages.
Though niacin is found in all sorts of places, the problem started with it’s original discovery using nicotine.
Organic Chemistry
1867, Huber provides the first description of nicotinic acid. 1873, Weidel describes the elemental analysis and crystalline structure of the salts etc.
These methods described by R Laiblin in 1879 page 808
http://www.rsc.org/delivery/_ArticleLinking/DisplayArticleForFree.cfm?doi=CA8793600775&JournalCode=CA
So the chemical had already been named,before they discovered its properties.
NICOTINIC ACID
Organic Syntheses, Coll. Vol. 1, p.385 (1941); Vol. 4, p.49 (1925).
http://www.orgsyn.org/orgsyn/prep.asp?prep=cv1p0385
When the properties of nicotinic acid started to be discovered this caused a huge problem to the anti-tobacco movement,who mistakenly thought that enriched bread would encourage cigarette use.
LAW – Enriched Flour and Bread – 1941
http://www.scstatehouse.net/code/t39c027.htm
“Niacin was first discovered from the oxidation of nicotine to form nicotinic acid.
When the properties of nicotinic acid were discovered, it was thought prudent to choose a name to dissociate it from nicotine, in order to avoid the perception that vitamins or niacin-rich food contains nicotine.
The resulting name ‘niacin’ was derived from nicotinic acid + vitamin.”
“Niacin is also referred to as Vitamin B3 because it was the third of the B vitamins to be discovered.
It has historically been referred to as “vitamin PP”, a name derived from the term “pellagra-preventing factor”.
http://www.chemie.de/lexikon/e/Niacin
“The term “niacin” used interchangeably with vitamin B3 is actually a non-technical term that refers to several different chemical forms of the vitamin.
These forms include nicotinic acid and nicotinamide. (Nicotinamide is also sometimes called niacinamide.) The names “niacin,” “nicotinic acid,” and “nicotinamide” are all derived from research studies on tobacco in the early 1930’s.
At that time, the first laboratory isolation of vitamin B3 occurred following work on the chemical nicotine that had been obtained from tobacco leaves.”
http://www.whfoods.com/genpage.php?tname=nutrient&dbid=83
So what happens if we take this small amount of topically applied niacin away, without the correct substitution?
“Are lung cancers triggered by stopping smoking?”
“The clinically high correlation between smoking and carcinoma of the lungs has been the focal point in societal campaigns against the habit and the tobacco lobby.”
“We are struck by the more than casual relationship between the appearance of lung cancer and an abrupt and recent cessation of the smoking habit in many, if not most, cases.”
Experience is their guide, numerically speaking. Of the 312 lung cancer patients they treated during a four-year period, 182 had recently quit smoking.
The report goes into detail. “Each had been addicted to the habit no less than 25 years, smoking in excess of 20 sticks a day. The striking direct statistical correlation between cessation of smoking to the development of lung malignancies, more than 60% plus, is too glaring to be dismissed as coincidental.”
http://www.guardian.co.uk/education/2007/oct/16/highereducation.research1
Which would seem a very good match to me.
Rose
Though niacin is found in all sorts of places, the problem started with it’s original discovery using nicotine.
Organic Chemistry
1867, Huber provides the first description of nicotinic acid. 1873, Weidel describes the elemental analysis and crystalline structure of the salts etc.
These methods described by R Laiblin in 1879 page 808
http://www.rsc.org/delivery/_ArticleLinking/DisplayArticleForFree.cfm?doi=CA8793600775&JournalCode=CA
So the chemical had already been named,before they discovered its properties.
NICOTINIC ACID
Organic Syntheses, Coll. Vol. 1, p.385 (1941); Vol. 4, p.49 (1925).
http://www.orgsyn.org/orgsyn/prep.asp?prep=cv1p0385
When the properties of nicotinic acid started to be discovered this caused a huge problem to the anti-tobacco movement,who mistakenly thought that enriched bread would encourage cigarette use.
LAW – Enriched Flour and Bread – 1941
http://www.scstatehouse.net/code/t39c027.htm
“Niacin was first discovered from the oxidation of nicotine to form nicotinic acid.
When the properties of nicotinic acid were discovered, it was thought prudent to choose a name to dissociate it from nicotine, in order to avoid the perception that vitamins or niacin-rich food contains nicotine.
The resulting name ‘niacin’ was derived from nicotinic acid + vitamin.”
“Niacin is also referred to as Vitamin B3 because it was the third of the B vitamins to be discovered.
It has historically been referred to as “vitamin PP”, a name derived from the term “pellagra-preventing factor”.
http://www.chemie.de/lexikon/e/Niacin
“The term “niacin” used interchangeably with vitamin B3 is actually a non-technical term that refers to several different chemical forms of the vitamin.
These forms include nicotinic acid and nicotinamide. (Nicotinamide is also sometimes called niacinamide.) The names “niacin,” “nicotinic acid,” and “nicotinamide” are all derived from research studies on tobacco in the early 1930’s.
At that time, the first laboratory isolation of vitamin B3 occurred following work on the chemical nicotine that had been obtained from tobacco leaves.”
http://www.whfoods.com/genpage.php?tname=nutrient&dbid=83
So what happens if we take this small amount of topically applied niacin away, without the correct substitution?
“Are lung cancers triggered by stopping smoking?”
“The clinically high correlation between smoking and carcinoma of the lungs has been the focal point in societal campaigns against the habit and the tobacco lobby.”
“We are struck by the more than casual relationship between the appearance of lung cancer and an abrupt and recent cessation of the smoking habit in many, if not most, cases.”
Experience is their guide, numerically speaking. Of the 312 lung cancer patients they treated during a four-year period, 182 had recently quit smoking.
The report goes into detail. “Each had been addicted to the habit no less than 25 years, smoking in excess of 20 sticks a day. The striking direct statistical correlation between cessation of smoking to the development of lung malignancies, more than 60% plus, is too glaring to be dismissed as coincidental.”
http://www.guardian.co.uk/education/2007/oct/16/highereducation.research1
Which would seem a very good match to me.
Rose
Chris
I read that study last night too, Chris. It is based on a Canadian sample of study data (meta-analysed IIRC).
Each calculation is only as reliable as the basic assumed mortality rate that you start with. Isn’t that the way of all sample-based (as opposed to population-based) statistics. I just used rates extrapolated from Doll’s samples.
Plus, of course, the mortality rate changes on a year-to-year basis, partly because the initial cohort is being gradually reduced and each new year’s annual mortality rate will be altered by an ever-increasing proportion of folk who started smoking after year 1 of the calculations.
It is really that imprecise. It should be clear that calculating such a lifetime risk will depend on your starting point (which of course determines the assumed ‘current’ mortality rate). Generally if you were to start now, and for a population in which LC incidence has been significantly reducing in recent years, then the lifetime risk will be calculated up to 40/50/60 years in the future, so is most likely to be much smaller than calculations that started (say) 20-30 years back, when mortality rates were generally higher.
In 2009 there were about 30,000 lung cancer deaths in England & Wales (offical ONS statistics). Someone might like to calculate what that means in terms of deaths per 100,000 smokers and compare the predicted lifetime risk from this. Anyone?
I can’t be arsed, to be honest, but my gut feel says it is likely to be slightly higher than Doll’s figures – so probably nearer to the Canadian ones.
Brian Bond
somewhat consistent with…
http://cebp.aacrjournals.org/content/15/8/1526.abstract
A Phase I Study of myo-Inositol for Lung Cancer Chemoprevention
Results: The maximum tolerated dose was found to be 18 g/d. Side effects, when present, were mild and mainly gastrointestinal in nature. Using the regression rate of the placebo subjects from a recently completed clinical trial with the same inclusion/exclusion criteria as a comparison, a significant increase in the rate of regression of preexisting dysplastic lesions was observed (91% versus 48%; P = 0.014). A statistically significant reduction in the systolic and diastolic blood pressures by an average of 10 mm Hg was observed after taking 18 g/d of myo-inositol for a month or more.
*****
From wiki — just to clarify
Myo-Inositol was once classified as a member of the vitamin B complex.[citation needed] However, because it is produced by the human body from glucose, it is not an essential nutrient. Some substances such as niacin can also be synthesized in the body, but are not made in amounts considered adequate for good health, and thus are still classified as essential nutrients. However, there is no convincing evidence that this is the case for myo-inositol.
Lifelong smoker LC proportion
Proportion of lifelong smokers who die of lung cancer:
Using Doll’s 2004 paper on his smoking doctors (1) I estimate the figure at 7% for lifelong cigarette smokers and 5% for pipe/cigar smokers. (This may appear contrary to RR values but I think this is because pipe smokers were older at death).
One problem with this estimate is that many of his study participants were still living and as lung cancer is a disease of old age the 7% figure is probably an underestimate. However I used the same method on his earlier (1994) paper and came up with 6.8% for cigarette smokers, so not much change in ten years.
I took his figures at face value so diagnosis bias would probably make it lower in reality.
Method of estimation:
I used table 1 and looked at the ‘Age standardised mortality rate per 1000 men/year’ for lung cancer and then divided it by the all cause figure. So for current cigarette smokers: 2.49/35.4 = 0.07.
Adjustments etc might make this estimate unreliable so I double checked by using it to calculate actual numbers of deaths for each category. e.g. for current smokers: %age * actual number (as given in table) is 0.07 * 4680 = 329 deaths.
Adding all the categories (smoker, former, non etc) together I estimated 1013 total deaths from lung cancer which compares pretty well with the total given of 1052.
References:
1. http://www.bmj.com/content/328/7455/1519.full.pdf+html?sid=70abdb58-c1f8-497f-a2cb-90c08e73c4f6
Tony
P.S. I also noticed a bizarre anomaly. In his 1994 paper he has 5280 current smoker deaths but by 2004 the number had shrunk to 4680. All other categories increased as you would expect. NB these are actual deaths for the entire cohort, not adjusted ones. So either he has changed the classification retrospectively or at least 600 current smokers came back from the dead!
In a number of posts people have pointed out the factor of diet; I have mentioned biological variation.
Firstly – it should not be too difficult to find foods containing an ample amount/day intake of this vitamin.
http://www.weightlossforall.com/foods-rich-vitamin-b6.htm
Secondly – looking at the numerous processes this vitamin is involved in.
(good old Wikipedia)
http://en.wikipedia.org/wiki/Vitamin_B6
looking at the various processes affected by this vitamin + the numerous knock on effects on other processes leads to the question can there really by only ONE MALFUNCTION for the genesis and manifestation of any given type of cancer?
Can’t see any more than the abstract there, unfortunately. Here’s another way of looking at Canada’s lung cancer incidence rates:
http://www.ncic.cancer.ca/Canada-wide/About%20cancer/Cancer%20statistics/Canadian%20Cancer%20Statistics/Special%20topics/Comparison%20of%20cancer%20in%20Canada%20from%201987%20to%201997.aspx?sc_lang=en#ccsfix
In 1987 there were 10721 lung cancer deaths in Canada. Assume that 85% of those are in smokers and ex-smokers, giving 9,113. In 1987, the Canadian population was around 25,500,000:
http://www12.statcan.ca/census-recensement/2006/as-sa/97-550/figures/c2-eng.cfm
Let’s say that 40%, or 10,200,000 are smokers or ex-smokers.
So, we can say that roughly 9,113 of these 10.2m smokers will be diagnosed with lung cancer each year. If we agree that lung cancer doesn’t really happen before 45 years and is mostly finished with by 85 years, then we have a 40 year risk period. So, 9,113 x 40 = 364,520. Then 364,520 ÷ 10.2m = 3.6%
It doesn’t matter where I do this calculation in the Western world, it keeps on coming out at around 3%-4%.
Anon (Gary again?),
The 10% figure is for lifelong smokers. Unless you have data for the number of lifelong smokers you won’t be able to get a fair estimate.
CJS
“The dose maketh the poison.”
1957
“Dr. E. L, Wynder of Sloan-Kettering Institute, a leading proponent of the cigarette theory of lung cancer, reported only this year that:
“The benzpyrene content of tobacco tar is not more than 2 parts per million which, according to our experiments, is not sufficient to produce the type of activity noted in our animals painted with tobacco tar.”
The substance frequently is produced in minute quantities in the burning of any organic compound and is present in varying degrees in city air.
Recent reports in England show that the daily intake of benzpyrene from breathing London air is equivalent in total volume to the intake from smoking about 100 cigarettes a day.”
http://tobaccodocuments.org/ctr/CTRMN043191-3193.html
Testimony of Dr Hueper 1957
“They manipulated the evidence. Anyone who introduces a corrective factor in his calculations to make the evidence fit a preconceived idea, I do not feel that this is valid scientific evidence.
“Do you feel, in view of what you said, that the application of a corrective factor means a predetermined manipulation in this case?
A.In this case I could not say, no.
Q I want to get clear on that.You asked me to read on. I will do that. This appears on Page 435 of your May, 1957 article and reads;
“However, even this estimate is heavily biased by the arbitrary assumption that the benzpyrene content present allegedly in cigarette smoke was about 12 times as effective in eliciting cancers as benzpyrene demonstrated in atmospheric air.
Only when such a “corrective” coefficient is applied was it possible to obtain proportional correlations between the total exposure to benzpyrene from both cigarette smoking and air pollutants and the relative incidence rates of lung cancer found in the industrialized metropolitan Liverpool area, an intermediary urban-rural region, and the rural area of North Wales”
A That is right.
Q That was your statement.
A I would like to have that on the record too.
Q All right. It is in Doctor”
http://tobaccodocuments.org/rjr/503243231-3367.html?zoom=750&ocr_position=above_foramatted&start_page=91
I’m not sure if this has been posted.
Auerbach’s Smoking Beagles [Discusses Response of A Dog to An Inhalation Experiment States That These Methods Produced A Carcinoma in the Animal]
“One dog, which was an inveterate smoker [?], was placed in a stall to demonstrate how the animal smoked.
We used a University Kentucky reference cigarette.
The dog’s handler, Mr. David Kirman, recognized the cigarette to be stronger than the brand they were using, and the behavior of the dog showed that he too was not used to this kind ofsmoke.
The lighting puff was not given to the dog but was made by the pump attached to the cigarette holder.
Thereafter the dog did its own smoking.
Counting the puff that the dog took and also looking at the records, it was obvious that the animal took between 20 to 30 shallow ones per cigarette.
The amount of smoke could be regulated by the attendant by pinching of the tube leading from the cigarette to the tracheostomy tube.
During the demonstration Mr Kirman did this when the dog became cyanotic,very restless, and salivated excessively.
During the smoking period which last 8-10 minutes, smoke poured out of the dog’s mouth and nose.
There were moments when the animal was in obvious distress.
Mr Kirman states that there are 40 dogs still smoking and that the tests will continue.”
http://tobaccodocuments.org/ctr/CTRMN043263-3264.html
Chilling.
Rose
Chilling indeed.
“Recent reports in England show that the daily intake of benzpyrene from breathing London air is equivalent in total volume to the intake from smoking about 100 cigarettes a day.””
Wonderful! Perfectly illustrates my point much earlier on about the components of tobacco smoke being the same as everyday air but in lower dosages.
Catch 15
Hello Dave.
Let us assume that benzo-pyrene is the molecule which causes lung cancer in smokers (via mutations of the p53 gene and other things).
Let us assume that a person smokes one cigarette per day absolutely regularly and fully inhales but blows out, and bearing in mind that ‘the dose is the poison’, how does the human body ‘metabolise’, or ‘neutralise’ or ‘dispose of’ the benzo-pyrene molecules which have been inhaled day after day at a rate represented by ‘one cigarette per day’? That is, of course, assuming that it is true that ‘the dose is the poison’.
Perhaps the human body does not ‘dispose of’ the BP molecules. Perhaps the dose is each individual molecule of BP and the dose is cumulative. Maybe each molecule of BP affects one individual cell, or half a cell, or two cells. But if that is true, why is it that lung tumours caused by smoking tend to be ‘lumps’ rather than spread out all over the lung?
It really is all very peculiar, isn’t it?
Perhaps you could explain. Of course, there could be no explanation. But it may be possible to show that SHS is so diluted that there are very few molecules of BP in the air. Bearing in mind the billions and billions of lung cells, the harmful effect of ‘the dose’ of the molecule may well be minuscule in reality.
I hope that what I have said above is realistic.
Catch 15
Hello Dave.
Let us assume that benzo-pyrene is the molecule which causes lung cancer in smokers (via mutations of the p53 gene and other things).
Let us assume that a person smokes one cigarette per day absolutely regularly and fully inhales but blows out, and bearing in mind that ‘the dose is the poison’, how does the human body ‘metabolise’, or ‘neutralise’ or ‘dispose of’ the benzo-pyrene molecules which have been inhaled day after day at a rate represented by ‘one cigarette per day’? That is, of course, assuming that it is true that ‘the dose is the poison’.
Perhaps the human body does not ‘dispose of’ the BP molecules. Perhaps the dose is each individual molecule of BP and the dose is cumulative. Maybe each molecule of BP affects one individual cell, or half a cell, or two cells. But if that is true, why is it that lung tumours caused by smoking tend to be ‘lumps’ rather than spread out all over the lung?
It really is all very peculiar, isn’t it?
Perhaps you could explain. Of course, there could be no explanation. But it may be possible to show that SHS is so diluted that there are very few molecules of BP in the air. Bearing in mind the billions and billions of lung cells, the harmful effect of ‘the dose’ of the molecule may well be minuscule in reality.
I hope that what I have said above is realistic.
Re: Catch 15
Indeed Junican that is why very light smokers, 2-3 a day do not have any higher risk of LC, mortality or heart disease.
Going back to Junican’s post of 4.26am yesterday. Is smokers’ lung cancer different to never smokers? From what I’ve read recently, including quotes from one of the authors of the work, I thought yes. But now it seems not. If a proportion of lung cancer among never smokers is of the “smokers type”, this could be attributed to passive smoking. Dave, have you anything more to say on this?
Going back to Junican’s post of 4.26am yesterday. Is smokers’ lung cancer different to never smokers? From what I’ve read recently, including quotes from one of the authors of the work, I thought yes. But now it seems not. If a proportion of lung cancer among never smokers is of the “smokers type”, this could be attributed to passive smoking. Dave, have you anything more to say on this?
“If a proportion of lung cancer among never smokers is of the “smokers type”, this could be attributed to passive smoking”
or more realistically, it could just show that smokers and non-smokers get the same disease, and that smokers’ lung cancer isn’t different at all – more common perhaps, but that means nothing until it’s shown smoking actually causes it. If it’s present in non-smokers, then the smoking isn’t causing it.
Never forget that this started as a little white lie, cooked up by our Chief Medical Officer in support Richard Doll’s study, the purpose of which appears to be to distract from the dreadful death toll from air pollution and industrial exposures.
Godber just took it further, though it was entirely unfounded on any science whatsoever.
It was just a means to an end.
“Godber recollected that he had said in 1962 to Keith Joseph, another of his Conservative ministers, that “we really have to do something about abolishing smoking” (having won the approval of the Health Minister Enoch Powell).
Joseph looked quite shocked and said: “You really can’t expect to abolish smoking.”
Godber replied: “No, but I want to see it reduced to an activity of consenting adults in private.”
“I can’t break with Godber,” wrote Crossman in his diary in October 1969. “He is a very powerful man of the department and people never like acting against his wishes.
He is away half of the time around the world, advising the World Health Organisation, in America, lecturing.
He is remote, out of touch now I think, except with the lord high panjandra and the physicians in the Royal Colleges of London.
He knows all the top people, but nothing about ordinary life, yet on the other hand he is radical and left-wing.
I don’t want to quarrel with him.”
http://tinyurl.com/2eqfdg5
As the results of the bans come in showing no change in heart attacks, they have to “correct” them to publish as a press release, to show that all the damage to society was worth it.
The “addictive nicotine” on which decades of propaganda campaign was based is now coming in with a 98.4 failure rate, another obvious “mistake”.
It is fine to believe that there are fairies at the bottom of the garden, but one should never attempt to catch and dissect them.
I think that they are just beginning to find this out.
Rose
Never forget that this started as a little white lie, cooked up by our Chief Medical Officer in support Richard Doll’s study, the purpose of which appears to be to distract from the dreadful death toll from air pollution and industrial exposures.
Godber just took it further, though it was entirely unfounded on any science whatsoever.
It was just a means to an end.
“Godber recollected that he had said in 1962 to Keith Joseph, another of his Conservative ministers, that “we really have to do something about abolishing smoking” (having won the approval of the Health Minister Enoch Powell).
Joseph looked quite shocked and said: “You really can’t expect to abolish smoking.”
Godber replied: “No, but I want to see it reduced to an activity of consenting adults in private.”
“I can’t break with Godber,” wrote Crossman in his diary in October 1969. “He is a very powerful man of the department and people never like acting against his wishes.
He is away half of the time around the world, advising the World Health Organisation, in America, lecturing.
He is remote, out of touch now I think, except with the lord high panjandra and the physicians in the Royal Colleges of London.
He knows all the top people, but nothing about ordinary life, yet on the other hand he is radical and left-wing.
I don’t want to quarrel with him.”
http://tinyurl.com/2eqfdg5
As the results of the bans come in showing no change in heart attacks, they have to “correct” them to publish as a press release, to show that all the damage to society was worth it.
The “addictive nicotine” on which decades of propaganda campaign was based is now coming in with a 98.4 failure rate, another obvious “mistake”.
It is fine to believe that there are fairies at the bottom of the garden, but one should never attempt to catch and dissect them.
I think that they are just beginning to find this out.
Rose
“If a proportion of lung cancer among never smokers is of the “smokers type”, this could be attributed to passive smoking”
or more realistically, it could just show that smokers and non-smokers get the same disease, and that smokers’ lung cancer isn’t different at all – more common perhaps, but that means nothing until it’s shown smoking actually causes it. If it’s present in non-smokers, then the smoking isn’t causing it.
Re: Catch 15
Indeed Junican that is why very light smokers, 2-3 a day do not have any higher risk of LC, mortality or heart disease.
That kind of betrayal is why the anti-smokers got away with it.
(p53 gene mutations are not required for early dissemination of cancer cells. S Offner, W Schmaus, K Witter, GB Baretton, G Schlimok, B Passlick, G Riethmuller, K Pantel. Proc Natl Acad Sci USA 1999 Jun;96(12):6942-6946). The authors compared the p53 status of primary and micrometastatic tumor cells, and found no correlation. Also, they found that “the disseminated carcinoma cells rarely accumulate mutated p53 protein and that 10 cell lines derived thereof did not harbor p53 mutations even in the presence of such mutations in the autologous primary tumors.” They believe that “malignant cells may leave the primary carcinoma at an early stage of its development when p53 is not mutated yet.”
http://www.pnas.org/cgi/content/full/96/12/6942
And, there is experimental evidence that polycyclic organic hydrocarbons and physiological conditions such as hypoxia select for cells with mutated p53. Polycyclic aromatic hydrocarbons inhibited growth of normal cells more than those whose p53 has been previously inactivated either by mutations or by HPV E6, the oncogenic protein of human papillomavirus. (Polycyclic aromatic hydrocarbons enhance terminal cell death of human ectocervical cells. EA Rorke, N Sizemore, H Mukhtar, LH Couch, PC Howard. Int J Oncol 1998 Sep;13(3):557-563)
http://www.ncbi.nlm.nih.gov/pubmed/9683793
MEANWHILE, as you stupidly endorse the anti-smokers’ junk science, they get away with flagrant scientific fraud for ignoring more than 50 studies, which show that human papillomaviruses cause at least a quarter of non-small cell lung cancers. Smokers and passive smokers are more likely to have been exposed to this virus, for socioeconomic reasons. And the anti-smokers’ studies are all based on nothing but lifestyle questionnaires, so they’re cynically DESIGNED to blame tobacco for all those extra lung cancers that are really caused by HPV. And those criminals commit the same type of fraud with every disease they blame on tobacco.
http://www.smokershistory.com/hpvlungc.htm
But perhaps you have a financial interest in peddling anti-smoker lies, because it helps you sell e-cigarettes.
http://blogs.bmj.com/bmj/2010/03/17/patrick-basham-the-doh-is-wrong-about-cessation/
That kind of betrayal is why the anti-smokers got away with it.
(p53 gene mutations are not required for early dissemination of cancer cells. S Offner, W Schmaus, K Witter, GB Baretton, G Schlimok, B Passlick, G Riethmuller, K Pantel. Proc Natl Acad Sci USA 1999 Jun;96(12):6942-6946). The authors compared the p53 status of primary and micrometastatic tumor cells, and found no correlation. Also, they found that “the disseminated carcinoma cells rarely accumulate mutated p53 protein and that 10 cell lines derived thereof did not harbor p53 mutations even in the presence of such mutations in the autologous primary tumors.” They believe that “malignant cells may leave the primary carcinoma at an early stage of its development when p53 is not mutated yet.”
http://www.pnas.org/cgi/content/full/96/12/6942
And, there is experimental evidence that polycyclic organic hydrocarbons and physiological conditions such as hypoxia select for cells with mutated p53. Polycyclic aromatic hydrocarbons inhibited growth of normal cells more than those whose p53 has been previously inactivated either by mutations or by HPV E6, the oncogenic protein of human papillomavirus. (Polycyclic aromatic hydrocarbons enhance terminal cell death of human ectocervical cells. EA Rorke, N Sizemore, H Mukhtar, LH Couch, PC Howard. Int J Oncol 1998 Sep;13(3):557-563)
http://www.ncbi.nlm.nih.gov/pubmed/9683793
MEANWHILE, as you stupidly endorse the anti-smokers’ junk science, they get away with flagrant scientific fraud for ignoring more than 50 studies, which show that human papillomaviruses cause at least a quarter of non-small cell lung cancers. Smokers and passive smokers are more likely to have been exposed to this virus, for socioeconomic reasons. And the anti-smokers’ studies are all based on nothing but lifestyle questionnaires, so they’re cynically DESIGNED to blame tobacco for all those extra lung cancers that are really caused by HPV. And those criminals commit the same type of fraud with every disease they blame on tobacco.
http://www.smokershistory.com/hpvlungc.htm
But perhaps you have a financial interest in peddling anti-smoker lies, because it helps you sell e-cigarettes.
http://blogs.bmj.com/bmj/2010/03/17/patrick-basham-the-doh-is-wrong-about-cessation/
That kind of betrayal is why the anti-smokers got away with it.
(p53 gene mutations are not required for early dissemination of cancer cells. S Offner, W Schmaus, K Witter, GB Baretton, G Schlimok, B Passlick, G Riethmuller, K Pantel. Proc Natl Acad Sci USA 1999 Jun;96(12):6942-6946). The authors compared the p53 status of primary and micrometastatic tumor cells, and found no correlation. Also, they found that “the disseminated carcinoma cells rarely accumulate mutated p53 protein and that 10 cell lines derived thereof did not harbor p53 mutations even in the presence of such mutations in the autologous primary tumors.” They believe that “malignant cells may leave the primary carcinoma at an early stage of its development when p53 is not mutated yet.”
http://www.pnas.org/cgi/content/full/96/12/6942
And, there is experimental evidence that polycyclic organic hydrocarbons and physiological conditions such as hypoxia select for cells with mutated p53. Polycyclic aromatic hydrocarbons inhibited growth of normal cells more than those whose p53 has been previously inactivated either by mutations or by HPV E6, the oncogenic protein of human papillomavirus. (Polycyclic aromatic hydrocarbons enhance terminal cell death of human ectocervical cells. EA Rorke, N Sizemore, H Mukhtar, LH Couch, PC Howard. Int J Oncol 1998 Sep;13(3):557-563)
http://www.ncbi.nlm.nih.gov/pubmed/9683793
MEANWHILE, as you stupidly endorse the anti-smokers’ junk science, they get away with flagrant scientific fraud for ignoring more than 50 studies, which show that human papillomaviruses cause at least a quarter of non-small cell lung cancers. Smokers and passive smokers are more likely to have been exposed to this virus, for socioeconomic reasons. And the anti-smokers’ studies are all based on nothing but lifestyle questionnaires, so they’re cynically DESIGNED to blame tobacco for all those extra lung cancers that are really caused by HPV. And those criminals commit the same type of fraud with every disease they blame on tobacco.
http://www.smokershistory.com/hpvlungc.htm
But perhaps you have a financial interest in peddling anti-smoker lies, because it helps you sell e-cigarettes.
http://blogs.bmj.com/bmj/2010/03/17/patrick-basham-the-doh-is-wrong-about-cessation/
Re: “What things in life matter most to you?”
I have an absolute right to smoke tobacco. Non smokers have an absolute right not to smoke tobacco. Whether antis like it or not doesn’t concern me, that’s all there is to it hence they are the ones permanently making the running.
Re: “What things in life matter most to you?”
I have an absolute right to smoke tobacco. Non smokers have an absolute right not to smoke tobacco. Whether antis like it or not doesn’t concern me, that’s all there is to it hence they are the ones permanently making the running.
Re: “What things in life matter most to you?”
I have an absolute right to smoke tobacco. Non smokers have an absolute right not to smoke tobacco. Whether antis like it or not doesn’t concern me, that’s all there is to it hence they are the ones permanently making the running.