A novel genetic polymorphism of inducible nitric oxide synthase is associated with an increased risk of gastric cancer

AIM: Inducible nitric oxide synthase (iNOS) plays a central role in the pathway of reactive oxygen and nitrogen species metabolism when Helicobacter pylori (H pylon) 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 (γ), 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). CONCLUSION: 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.

E-cadherin gene C-160A promoter polymorphism and risk of non-cardia gastric cancer in a Chinese population

AIM: To test the hypothesis that E-cadherin gene (CDH1)C-160A promoter variant genotype is associated with an increased risk for developing gastric cancer.METHODS: In this population-based case-control study of gastric cancer in Jiangsu Province, China, we performed polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to genotype the C-160A polymorphism of CDH1 promoter in 206 non-cardia gastriccancer patients and 261 age- and sex-matched but unrelated cancer-free controls.RESULTS: The frequencies of genotypes CC, CA and AA were 57.8%, 36.4% and 5.8% in gasfric cancer cases,respectively, and 58.2%, 34.9% and 6.9% in controls respectively. The distributions of CDH1 genotypes were not significantly different between gastric cancer cases and controls (P = 0.87 for genotype frequency and P = 0.92for allele frequency). Compared with the CC genotype, the CA and AA genotypes were not associated with an increased risk for non-cardia gastric cancer (adjusted odds ratios (OR)= 1.15, and 95% confidence interval (95% CI) = 0.78-1.72for CA genotype, and OR = 0.90 and 95% CI = 0.42-2.01for AA genotype).CONCLUSION: E-cadherin gene C-160A promoter polymorphism may not play a major role in the etiology of non-cardia gastric cancer in Chinese population.