Glutathione S-transferase T1 and M1 polymorphisms are associated with lung cancer risk in a gender-specific manner

Glutathione S-transferase (GST) T1 and M1 are detoxification enzymes which neutralize various carcinogenic compounds. Polymorphisms of the GSTT1 and GSTM1 genes which encode the enzymes could be associated with cancer risk.

We investigated the association of GSTT1 and GSTM1 null polymorphisms with lung cancer risk in a tightly matched, considerably large sample in China. Genotyping was performed utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and DNA sequencing, and associations were measured by using logistic regression analysis.

We found that the null genotypes of both polymorphisms resulted in an increased lung cancer risk, with an odds ratio (OR) of 1.57 (95% confidence interval (CI) 1.23-2.00) for GSTT1 and OR 1.87 (95% CI 1.46-2.39) for GSTM1 (p < 0.01). Significant associations remained after stratification by histopathology (p < 0.01) and smoking status (p < 0.05). When gender-stratified association was performed, we found that the GSTT1 null genotype resulted in an increased risk among males (adjusted OR 2.95, 95% CI 2.07-4.20; p < 0.01) but not females (p > 0.05), while the GSTM1 null genotype resulted in an increased risk among females (adjusted OR 2.18, 95% CI 1.54-3.10; p < 0.01) but not males (p < 0.05).

Polymorphisms in GSTT1 and GSTM1 are associated with the risk of lung cancer in a gender-specific manner.