TNF-α-308/-238 polymorphisms are associated with gastric cancer: A case-control family study in China

Associations of TNF-α-308 (rs1800629) and -238 (rs361525) with gastric cancer had the inconsistent indication among different populations.

In this case-control family study, 47 families were determined with the probands diagnosed with gastric cancer (case family, n=296), accordingly 47 families without gastric cancer were matched with the case families by multivariate distribution of age, sex, social class, and pedigree size (control family, n=319). Polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR) was used to identify the TNF genotype. Chi-square test was used to compare the groups regarding genotype and the allele frequencies, HWE test for Hardy-Weinberg equilibrium.

The frequencies of TNF-α-308 GA and AA genotypes were significantly higher in case family than that in control family. The risk of gastric cancer was increased in GA and AA carriers in the first degree (OR=2.06, 95% CI=1.20-3.51 and OR=4.89, 95% CI=2.74-8.74), however the similar result was not found in the second degree. Helicobacter pylori infection status were significantly associated with risk of gastric cancer in first-degree relatives (OR=1.96, 95% CI=1.26-3.05) while no statistical significance was noted in the second-degree relatives. Haplotypes of TNF-α-308/-238 alleles, GA/GG, AA/GG and AA/GA indicated the susceptibilities to gastric cancer with OR and 95% confident intervals resulting 2.07 (1.34-3.21), 4.49 (2.74-7.33) and 4.98 (1.76-14.01) respectively.

TNF-α-G308A (rs1800629) polymorphisms are associated with gastric cancer in Chinese population. Haplotypes of TNF-α-308/-238 GA/GG, AA/GG and AA/GA increase the susceptibilities to gastric cancer. The first-degree relatives are more likely to develop into gastric cancer with TNF-α-G308 polymorphisms and H. pylori positive than the second-degree are.