title: Repair of tobacco carcinogen-induced DNA adducts and lung cancer risk: a molecular epidemiologic study.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Epidemiology, Division of Cancer Prevention, The University of Texas M. D. Anderson Cancer, Houston, Texas 77030, USA. qwei@mdanderson.org
authors.forename: Q
authors.initials: Q
authors.lastname: Wei
authors.forename: L
authors.initials: L
authors.lastname: Cheng
authors.forename: C I
authors.initials: CI
authors.lastname: Amos
authors.forename: L E
authors.initials: LE
authors.lastname: Wang
authors.forename: Z
authors.initials: Z
authors.lastname: Guo
authors.forename: W K
authors.initials: WK
authors.lastname: Hong
authors.forename: M R
authors.initials: MR
authors.lastname: Spitz
mesh_terms: D000367:Age Factors; D000368:Aged; D002273:Carcinogens / Q000009:adverse effects*; D016022:Case-Control Studies; D002460:Cell Line; D018736:DNA Adducts / Q000187:drug effects / Q000235:genetics*; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D008214:Lymphocytes; D008297:Male; D008875:Middle Aged; D010957:Plasmids; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects*; D013781:Texas / Q000453:epidemiology; D014162:Transfection
chemical_list: D002273:Carcinogens; D018736:DNA Adducts