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.