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.
Wideroff
Louise
L
Applied Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, EPN 4005, 6130 Executive Boulevard, MSC 7344, Bethesda, MD 20892-7344, USA. Wideroff@nih.gov
Vaughan
Thomas L
TL
Farin
Federico M
FM
Gammon
Marilie D
MD
Risch
Harvey
H
Stanford
Janet L
JL
Chow
Wong-Ho
WH
D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000483:Alleles; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D014481:United States
D001191:Arylamine N-Acetyltransferase; D019363:Cytochrome P-450 CYP1A1; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D007527:Isoenzymes; C089384:N-acetyltransferase 1; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human