GST, NAT1, CYP1A1 polymorphisms and risk of esophageal and gastric adenocarcinomas.

Background: Polymorphisms in glutathione-S-transferase (GST), N-acetyltransferase (NAT) 1, and CYP1A1 genes have been suggested as susceptibility factors for esophageal and gastric adenocarcinomas, but have not been consistently linked to elevated risks. In a population-based case-control study, we examined risks in relation to polymorphisms of the following genes: GSTP1; GSTM1; GSTT1; NAT1; and CYP1A1.

Methods: Histologically confirmed incident cases, ages 30-79, were identified in three US locations. Population controls from the same catchment areas were frequency matched to expected age and sex distributions of esophageal and gastric cardia adenocarcinomas. DNA was extracted from buffy coat for PCR-based assays, with interpretable genotyping results obtained from 209 controls, 67 esophageal adenocarcinomas, 60 gastric cardia adenocarcinomas, and 56 noncardia gastric adenocarcinomas. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated among whites, adjusting for age, sex, and study center.

Results: In all histologic subgroups, ORs were somewhat elevated for the GSTP1 Val/Val genotype (versus Ile/Ile), although 95% CIs included 1.00. The respective ORs for esophageal, cardia, and other gastric adenocarcinomas were 1.73 (0.75-4.02), 1.46 (0.57-3.73), and 1.22 (0.48-3.09). No consistent patterns of elevated risk were associated with the null GSTM1 or GSTT1 genotypes, one or two copies of NAT110 or 11 alleles, or CYP1A1 Val/Val or Ile/Val genotypes (versus Ile/Ile).

Conclusions: Additional research in larger samples is needed to further assess polymorphisms and their interactions with epidemiologic risk factors, particularly for esophageal adenocarcinoma, which has been increasing markedly in incidence.