Copy Number Variants of GSTM1 and GSTT1 in Relation to Lung Cancer Risk in a Prospective Cohort Study

Abstract

Previous studies did not discriminate wild-type from hemizygous genotypes of GSTM1 and GSTT1. In this study, we investigated wild-type, hemizygous deletion, and homozygous deletion genotypes of GSTM1 and GSTT1 and lung cancer risk. We conducted a nested case-control study of 143 primary incident lung cancer cases matched to 447 cancer-free controls. Genotyping was carried out using a real-time polymerase chain reaction (PCR)-based assay. Conditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI). Compared to GSTM1 wild-type carriers, the relative odds of lung cancer increased from 1.49 (95% CI=0.66-3.40) to 1.80 (95% CI=0.81-4.02) for the hemizygous and homozygous deletion genotypes, respectively (p-trend=0.13). The strongest associations were seen among those who smoked less than one pack per day and had greater than or equal to one deletion variant of GSTM1 (OR=3.25; 95% CI=0.93-11.34; p-trend=0.07) whereas the reverse was observed for smokers who smoked greater than or equal to one pack per day (OR=0.80; 95% CI=0.24-2.67; p-interaction=0.08). No clear associations were observed for GSTT1 genotypes. Risk of lung cancer increased as the number of deletion variants increased for GSTM1, although the associations were nonsignificant. Discriminating between the wild-type, hemizygous, and homozygous deletion GSTM1 genotypes permitted a more precise characterization of the associations between GSTM1 deletion variants and lung cancer.