Smoking, DNA repair capacity and risk of nonsmall cell lung cancer.
Tobacco-related carcinogens cause a variety of DNA damage that is repaired by different enzymatic pathways, suggesting that DNA repair plays an important role in tobacco-induced carcinogenesis. In a large hospital-based case-control study, we investigated DNA repair capacity (DRC) as a biomarker for susceptibility to nonsmall cell lung cancer (NSCLC) and evaluated the possible interaction between DRC and tobacco smoke in 467 newly diagnosed NSCLC patients and 488 cancer-free controls. We measured DRC in cultured peripheral lymphocytes using the host-cell reactivation assay with a reporter gene damaged by an activated tobacco carcinogen, benzo[a]pyrene diol epoxide. The results showed that current smokers exhibited the highest DRCs as compared to former and nonsmokers both among patients and control subjects. There were no differences of DRC among 3 different histopathologic types of NSCLC. Logistic regression analysis revealed that suboptimal DRC and pack-years smoked were independent predictors of NSCLC risk. The overall 15.5% reduction in DRC observed in the cases (7.84%) compared to the controls (9.28%) (p<0.001) was associated with an approximately 2-fold increased risk of NSCLC (adjusted odds ratio (OR) = 1.85, 95% confidence interval (CI) 1.42-2.42). There was a significant dose-response association between decreased DRC and increased risk of lung cancer. Furthermore, we observed a nonstatistically significant additive but not multiplicative interaction between DRC and pack-years smoked on lung cancer risk, particularly in the histopathologic types of NSCLC other than adenocarcinoma. The results suggest that suboptimal DRC is associated with increased risk of NSCLC and DRC may modulate the risk of lung cancer associated with smoking but the latter needs to be verified in larger studies.
Shen
Hongbing
H
Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Spitz
Margaret R
MR
Qiao
Yawei
Y
Guo
Zhaozheng
Z
Wang
Li-E
LE
Bosken
Carol H
CH
Amos
Christopher I
CI
Wei
Qingyi
Q
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D018736:DNA Adducts / Q000187:drug effects; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*
D014408:Biomarkers, Tumor; D018736:DNA Adducts; D004273:DNA, Neoplasm