A novel genetic polymorphism of inducible nitric oxide synthase is associated with an increased risk of gastric cancer.
OBJECTIVE
Inducible nitric oxide synthase (iNOS) plays a central role in the pathway of reactive oxygen and nitrogen species metabolism when Helicobacter pylori (H pylori) infection occurs in humans. iNOS Ser(608)Leu allele, a novel genetic polymorphism (C/T) occurring within exon 16 of the iNOS reductase domain, may have a dramatic effect on the enzymatic activity. The aim of this study was to determine whether iNOS C/T polymorphism was associated with increased susceptibility to gastric cancer.


METHODS
We conducted a population based case-control study in a high gastric cancer incidence area, Yangzhong, China. Questionnaires from 93 patients with intestinal type gastric cancer (IGC), 50 with gastric cardia cancer (GCC) and 246 healthy controls were obtained between 1997 and 1998, and iNOS genotyping was carried out. Odds ratios (ORs), interaction index (gamma), and 95% confidence intervals for the combined effects of iNOS genotype and H pylori infection, cigarette smoking or alcohol drinking were estimated.


RESULTS
The frequency of (CT+TT) genotypes was higher in cases than in control group (24.48% vs 23.17%), but the difference was not statistically significant. After adjusting for age and gender, past cigarette smokers with (CT+TT) genotypes had a significantly increased risk of IGC (OR = 3.62, 95% CI: 1.23-10.64), while past alcohol drinkers with (CT+TT) genotypes had a significantly increased risk of GCC (OR = 3.33, 95% CI: 1.14-9.67). H pylori CagA negative subjects with (CT+TT) genotypes had a significantly increased risk of both IGC and GCC (OR = 2.19 and 3.52, respectively).


CONCLUSIONS
iNOS Ser(608)Leu allele may be a potential determinant of susceptibility to cigarette -alcohol induced gastric cancer, but larger studies are needed to confirm the observations.
Shen
Jing
J
Department of Epidemiology & Biostatistics, School of Public Health, Nanjing Medical University, Jiangsu Province, China. js2182@columbia.edu
Wang
Run-Tian
RT
Wang
Li-Wei
LW
Xu
Yao-Chu
YC
Wang
Xin-Ru
XR
D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D017354:Point Mutation; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D013274:Stomach Neoplasms / Q000453:epidemiology* / Q000235:genetics*
C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II