TNF-α and TNF-β polymorphisms with susceptibility to gastric cancer in a Korean population

Tumor necrosis factors (TNF) regulate the inflammatory response, cell growth and differentiation and its genetic polymorphisms are correlated with various cancer types including colon, and ovarian cancer. To determine whether polymorphisms at TNFA -G308A and TNFB +G252A were associated with a susceptibility to gastric cancer, we investigated the genotype and allele frequencies of these genes in 181 gastric cancer patients and 290 healthy individuals. The polymorphism analysis was performed by amplifying the promoter region of TNF-α for TNFA -308 and the first intron of TNF-β for TNFB +252, digestion with NCO1 restriction enzymes, and then sequencing the products. The frequencies of the genotypes for TNFA -308 were G/G, G/A, and A/A, 93.4% (169/181), 5.0% (9/181) and 1.7% (3/181), respectively, in gastric cancer patients and 88.6% (257/290), 11.4% (33/290) and 0% (0/290), respectively, in the healthy controls. Statistically, there was a significant difference in the genotype frequency of the TNFA -308 between the healthy controls and the gastric cancer patients (P=0.0034). However, genotype and allele frequency for TNFB +252 was not associated with an increased risk of gastric cancer in this population. When stratified by histological subtype of gastric cancer, there was no statistical significance between the risk and the two polymorphisms of TNFA -308 and TNFB +252. Our findings suggest that the TNFA -308 polymorphism of the TNF-α gene may be closely associated with susceptibility to gastric cancer in Korean patients. © 2010 The Korean Society of Toxicogenomics and Toxicoproteomics and Springer Netherlands.