Inducible nitric oxide synthetase genotype and Helicobacter pylori infection affect gastric cancer risk

World J Gastroenterol. 2012 Sep 21;18(35):4917-24. doi: 10.3748/wjg.v18.i35.4917.

Abstract

Aim: To investigate the association of the inducible nitric oxide synthetase (iNOS) C150T polymorphism with Helicobacter pylori (H. pylori) infection and gastric cancer (GC) risk in Iran.

Methods: In order to determine whether there was a correlation between iNOS genotype and GC in Iran, we conducted a case-control study using samples from 329 individuals. For each sample, the C150T iNOS polymorphism was genotyped by polymerase chain reaction (PCR) and restriction digestion. Patients were grouped by cancer presence, demographic and behavior characteristics, and H. pylori infection status. Statistical tests were conducted to determine whether any behavioral factors or a particular iNOS genotype was associated with GC in the study population.

Results: In this population, we found that smoking, hot beverage consumption, a familial history of GC and H. pylori infection status were significantly associated with GC development (P = 0.015, P < 0.001, P = 0.0034, and P < 0.015, respectively). The distribution of the C150T iNOS genotypes among the two study groups was not statistically significant alone, but was impacted by H. pylori infection status. When compared to the non-H. pylori infected group, cancer patients who had a heterozygous CT genotype and were also infected with H. pylori were 2.1 times more at risk of developing GC [odds ratio (OR) = 2.1, P = 0.03] while those with a homozygous TT genotype and infected with H. pylori were 5.0 times more at risk of developing GC (OR = 5.0, P = 0.029). In contrast, this association was not seen in patients in the control group.

Conclusion: A CT or TT polymorphism at position 150 in the iNOS gene significantly increases the risk of GC and may be a marker for GC susceptibility.

Keywords: Gastric cancer; Helicobacter pylori; Heterozygous CT genotype; Homozygous TT genotype; Inducible nitric oxide synthetase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Beverages / adverse effects
  • Case-Control Studies
  • Chi-Square Distribution
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Helicobacter Infections / epidemiology*
  • Helicobacter Infections / microbiology
  • Helicobacter pylori / pathogenicity*
  • Heterozygote
  • Homozygote
  • Hot Temperature
  • Humans
  • Iran / epidemiology
  • Logistic Models
  • Male
  • Middle Aged
  • Nitric Oxide Synthase Type II / genetics*
  • Odds Ratio
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Risk Assessment
  • Risk Factors
  • Smoking / adverse effects
  • Stomach Neoplasms / epidemiology*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / microbiology

Substances

  • NOS2 protein, human
  • Nitric Oxide Synthase Type II