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

• Published in: JNCI : Journal of the National Cancer Institute Vol. 92; no. 21; pp. 1764 - 1772
• Main Authors: Qingyi Wei, Lie Cheng, Amos, Christopher I., Wang, Li-E., Zhaozheng Guo, Hong, Waun K., Spitz, Margaret R.
• Format: Journal Article
• Language: English
• Published: Cary, NC Oxford University Press 01.11.2000
• Subjects: Age Factors; Aged; Biological and medical sciences; Carcinogens - adverse effects; Case-Control Studies; Cell Line; DNA Adducts - drug effects; DNA Adducts - genetics; DNA Repair - drug effects; DNA Repair - genetics; Dose-Response Relationship, Drug; Female; Humans; Logistic Models; Lung Neoplasms - epidemiology; Lung Neoplasms - etiology; Lung Neoplasms - genetics; Lymphocytes; Male; Medical sciences; Middle Aged; Plasmids; Pneumology; Sex Factors; Smoking - adverse effects; Texas - epidemiology; Transfection; Tumors of the respiratory system and mediastinum; United States; North America; America; Texas; Human; Lung disease; Respiratory disease; Tobacco smoking; Malignant tumor; Bronchopulmonary; Carcinogen; DNA; Risk factor; Molecular epidemiology; Bronchus disease; Genetics; Repair; Public health; Molecular adduct
• ISSN: 0027-8874; 1460-2105; 1460-2105
• DOI: 10.1093/jnci/92.21.1764

Background: Only a fraction of cigarette smokers develop lung cancer, suggesting that people differ in their susceptibility to this disease. We investigated whether differences in DNA repair capacity (DRC) for repairing tobacco carcinogen-induced DNA damage are associated with differential susceptibility to lung cancer. Methods: From August 1, 1995, through April 30, 1999, we conducted a hospital-based, case–control study of 316 newly diagnosed lung cancer patients and 316 cancer-free control subjects matched on age, sex, and smoking status. DRC was measured in cultured lymphocytes with the use of the host-cell reactivation assay with a reporter gene damaged by a known activated tobacco carcinogen, benzo[a]pyrene diol epoxide. Statistical tests were two-sided. Results: Overall, lower DRC was observed in case patients than in control subjects (P<.001) and was associated with a greater than twofold increased risk of lung cancer. 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 (odds ratio [OR] = 1.8 with 95% confidence interval [CI] = 1.1–3.1, OR = 2.0 with 95% CI = 1.2–3.4, and OR = 4.3 with 95% CI = 2.6–7.2 for the second, third, and fourth quartiles, respectively; Ptrend<.001). Case patients who were younger at diagnosis (<60 years old), female, or lighter smokers or who reported a family history of cancer exhibited the lowest DRC and the highest lung cancer risk among their subgroups, suggesting that these subgroups may be especially susceptible to lung cancer. Conclusion: The results provide evidence that low DRC is associated with increased risk of lung cancer. The findings from this hospital-based, case–control study should be validated in prospective studies.