Reduced expression levels of nucleotide excision repair genes in lung cancer: a case-control analysis

Epidemiological studies have indicated that reduced DNA repair capacity and increased DNA adduct levels are associated with increased risk of lung can cer, Nucleotide excision repair (NER) is the major pathway in humans for re pairing DNA adducts induced by smoking-related carcinogens, such as benzo[a ]pyrene diol epoxide, We hypothesized that genetically determined baseline expression level of genes involved in NER is associated with risk of lung c ancer. In a pilot case-control study, we measured the relative expression l evels of five NER genes [ERCC1, XPB/ERCC3, XPG/ERCC5, CSB/ERCC6 and XPC (ER CC, excision repair cross-complementing; CSB, Cockayne's syndrome complemen tary group B)] in phytohemagglutininstimulated peripheral lymphocytes obtai ned from 75 lung cancer patients and 95 controls using a newly developed mu ltiplex RT-PCR assay. Cases and controls were matched on age, sex, ethnicit y and tobacco use. The expression level of the p-actin gene was used as an internal control for the relative quantitation, We observed a 12.2 and 12.5 % decrease in the baseline expression levels of XPG/ERCC5 and CSB/ERCC6, re spectively, in cases compared with controls. These differences were statist ically significant (P < 0.01) when the median expression level in the contr ols was used as the cut-off point, the lung cancer patients were significan tly more likely than the controls to have reduced expression levels of XPG/ ERCC5 [odds ratio (OR), 2.32; 95% confidence interval (CI), 1.22-4.43] and CSB/ERCC6 (OR, 2.49; 95% CI, 1.28-4.84). There was also a dose-response rel ationship between reduced expression levels and increased lung cancer risk (trend test: P < 0.01). Our results suggest that individuals whose expressi on levels of XPG/ERCC5 and CSB/ERCC6 are reduced may be at higher risk of l ung cancer.