Abstract:
: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.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Shen H,Spitz MR,Qiao Y,Guo Z,Wang LE,Bosken CH,Amos CI,Wei Qdoi
10.1002/ijc.11346keywords:
subject
Has Abstractpub_date
2003-10-20 00:00:00pages
84-8issue
1eissn
0020-7136issn
1097-0215journal_volume
107pub_type
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