Gastric cancer susceptibility is not linked to pro-and anti-inflammatory cytokine gene polymorphisms in whites: a Nationwide Multicenter Study in Spain

Am J Gastroenterol. 2007 Sep;102(9):1878-92. doi: 10.1111/j.1572-0241.2007.01423.x. Epub 2007 Jul 19.

Abstract

Background and aims: Recent studies have reported an association between cytokine gene polymorphisms and GC risk. However, results are inconsistent among studies from different geographic regions and ethnic groups. Our goal was to evaluate the influence of Helicobacter pylori (H. pylori) infection and host genetic factors on GC susceptibility in a population of Spanish white GC patients.

Methods: DNA from 404 unrelated patients with GC and 404 sex- and age-matched healthy controls was typed for several functional polymorphisms in pro- (IL-1B, TNFA, LTA, IL-12p40) and anti-inflammatory (IL-4, IL-1RN, IL-10, TGFB1) genes by PCR, RFLP, and TaqMan assays. H. pylori infection and CagA/VacA antibody status were also determined by western blot serology.

Results: Logistic regression analysis identified H. pylori infection with cagA strains (OR 2.54, 95% CI 1.77-3.66), smoking habit (OR 1.91, 95% CI 1.25-2.93), and positive family history of GC (OR 3.67, 95% CI 2.01-6.71) as independent risk factors for GC. None of the cytokine gene polymorphisms analyzed in this study were associated with susceptibility to GC development, whether GC patients were analyzed as a group or categorized according to anatomic location or histological subtype. Some simultaneous combinations of proinflammatory genotypes reportedly associated with greater GC risk yielded no significant differences between patients and controls.

Conclusions: Our results show that, at least in some white populations, the contribution of the cytokine gene polymorphisms evaluated in this study (IL-1B, IL-1RN, IL-12p40, LTA, IL-10, IL-4, and TGF-B1) to GC susceptibility may be less relevant than previously reported.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Bacterial / analysis
  • Bacterial Proteins / analysis
  • Cytokines / genetics*
  • European Continental Ancestry Group
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Haplotypes
  • Helicobacter Infections / complications
  • Helicobacter Infections / diagnosis
  • Helicobacter pylori / genetics
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Spain
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / microbiology

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • Cytokines
  • VacA protein, Helicobacter pylori
  • cagA protein, Helicobacter pylori