The association between variant alleles of GSTM1 and GSTT1 and lung cancer risk: a nested case-control study in Washington County, Maryland Free

B14

Background: Polymorphic GSTM1 and GSTT1 genes regulate the detoxification of tobacco-related carcinogens and may play a role in lung carcinogenesis. Extensive studies have investigated the association between GSTM1 and GSTT1 and lung cancer risk. However, traditional genotyping assays were unable to discriminate between homozygous wild-type +/+ and heterozygous +/0 individuals and phenotypic differences in enzymatic activity associated with these genotypes may modulate lung cancer risk. In this study, we used a recently developed genotyping assay to investigate the associations between copy number variant alleles of GSTM1 and GSTT1 and lung cancer risk.
 >Methods: We conducted a case-control study nested in a well-characterized, community-based cohort. First-time diagnoses of lung cancer (n=137) were matched to cancer-free controls (n=441) on age, gender, and cigarette smoking history. DNA obtained from blood samples provided at baseline was genotyped using real-time PCR-based assay. Conditional logistic regression models were used to estimate Odds Ratios (ORs) and 95% Confidence Intervals (CIs).
 >Results: Compared to those with the GSTM1 homozygous wild-type 0/0, the relative odds of lung cancer increased from 1.49 (95% CI: 0.66-3.40) to 1.80 (95% CI: 0.81-4.01) for the GSTM1 +/0 and 0/0 genotypes, respectively (p-value for trend: 0.13). When stratified by smoking intensity, the risk associations were primarily concentrated among lighter smokers (OR: 3.25; 95% CI: 0.93-11.34 for ≥1 variant GSTM1 alleles). The results for GSTT1 were null.
 >Conclusions: Additional variant alleles of GSTM1were not strongly associated with the risk of lung cancer overall, but the risks were more pronounced among lighter cigarette smokers. GSTM1 variant alleles may have a more discernable impact on lung cancer susceptibility under circumstances when the dose of exposure to carcinogens is less. The results for GSTM1 suggest that new genotyping assays that classify those heterozygous from those homozygous for variant alleles will allow the roleof GSTs in lung carcinogenesis to be more precisely characterized.