It is widely accepted that tobacco
smoke is responsible for the vast majority of
lung cancers worldwide. There are many known and suspected
carcinogens present in cigarette
smoke, including alpha-emitting
radioisotopes. Epidemiologic studies have shown that increased
lung cancer risk is associated with exposure to ionizing radiation, and it is estimated that the majority of smoking-induced
lung cancers may be at least partly attributable to the inhaled and deposited radiation dose from
radioisotopes in the cigarette
smoke itself. Recent research shows that silencing of the tumor suppressor gene
p16(INK4a) (p16) by promoter methylation plays a role in smoking-related
lung cancer. Inactivation of p16 has also been associated with
lung cancer incidence in radiation-exposed workers, suggesting that
radionuclides in cigarette
smoke may be acting with other compounds to cause smoking-induced
lung cancer. We evaluated the mechanism of ionizing radiation as an accepted cause of
lung cancer in terms of its dose from tobacco
smoke and silencing of p16. Because both radiation and cigarette smoking are associated with inactivation of p16, and p16 inactivation has been shown to play a major role in
carcinogenesis, ionizing radiation from cigarette
smoke likely plays a role in
lung cancer risk. How large a role it plays, relative to chemical
carcinogens and other modes of action, remains to be elucidated.