Repair of Tobacco Carcinogen-Induced DNA Adducts and Lung Cancer Risk: a Molecular Epidemiologic Study

We investigated whether differences in DNA repair capacity for repairing tobacco carcinogen-induced DNA damage are associated with differential susceptibility to lung cancer

Qingyi Wei


Scholarcy highlights

  • A fraction of cigarette smokers develop lung cancer, suggesting that people differ in their susceptibility to this disease
  • With the use of the highest quartile as the referent group, those individuals of the entire 632-subject population who were in the lowest quartile had a more than fourfold increased risk of lung cancer; individuals under 60 years of age had an odds ratios of 4.9, females had an OR of 7.6, individuals who had smoked fewer than 40 pack-years had an OR of 4.8, and individuals who had a positive family history of cancer had an OR of 6.3. These findings are consistent with the notion that a fraction of lung cancer patients are especially susceptible to tobacco carcinogen-induced DNA damage due to suboptimal DNA repair. In this large molecular epidemiologic study of DNA repair capacity in lung cancer, which we believe to be the first of its kind, we demonstrated that reduced DRC had a statistically significant effect on risk of lung cancer after controlling for potential confounding variables and covariates
  • The DRC assay might be influenced by other, unmeasured confounding factors, the relatively large sample size, matching design, and consistent differences observed in the DRC of case patients and control subjects in all of the subgroups analyzed suggest that the results are unlikely to be spurious
  • They strongly support the hypothesis that reduced DRC is associated with increased risk of lung cancer
  • The finding of a dose-dependent association between decreased DRC and increased risk further strengthens the biologic plausibility of our hypothesis
  • Compared with the highest DRC quartile in the control subjects and after adjustment for age, sex, pack-years of smoking, family history of cancer, and other covariates, reduced DRC was associated with increased risk of lung cancer in a dose-dependent fashion
  • The nearly fourfold increased risk of lung cancer among individuals, regardless of smoking status, whose DRC falls in the lowest quartile is consistent with the notion that a fraction of the population is predisposed to lung cancer
  • The finding of an increase in DNA repair capacity with smoking is consistent with our previous finding that, in head and neck cancer patients, DNA repair gene expression was increased in the heavy smokers among both case patients and control subjects relative to the lighter smokers

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