TY - JOUR
T1 - Repair of tobacco carcinogen-induced DNA adducts and lung cancer risk
T2 - A molecular epidemiologic study
AU - Wei, Qingyi
AU - Cheng, Lie
AU - Amos, Christopher I.
AU - Wang, Li E.
AU - Guo, Zhaozheng
AU - Hong, Waun K.
AU - Spitz, Margaret R.
PY - 2000/11/1
Y1 - 2000/11/1
N2 - 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; P(trend)<.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.
AB - 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; P(trend)<.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.
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M3 - Article
C2 - 11058619
AN - SCOPUS:0034332586
SN - 0027-8874
VL - 92
SP - 1764
EP - 1772
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 21
ER -