Role of tumor necrosis factor-alpha -308 G/A promoter polymorphism in gastric cancer

ABSTRACT

Gastric cancer [GC] is the fourth most common cancer and the second most common cause of cancer death world-wide after lung cancer. It is a multifactorial disease with the involvement of both genetic and environmental risk factors. Genetic variation in genes encoding cytokines and their receptors, determine the intensity of the inflammatory response, which may contribute to individual differences in severity of outcome of the disease. Tumor necrosis factor alpha [TNF- alpha] is a potent pro-inflammatory cytokine and acid inhibitor. A bi allelic G to A polymorphism at -308 upstream from the transcription initiation site of the promoter is associated with elevated TNF levels. The present study is aimed at evaluating the role of TNF- alpha-308 [G [rightwards arrow] A] gene polymorphism and susceptibility to GC. A case-control study was carried out in 114 GC patients and 229 healthy control subjects. TNF- alpha genotyping at position-308 [G [rightwards arrow] A] was carried out by amplification refractory mutation system-polymerase chain reaction [ARMS-PCR] method followed by agarose gel electrophoresis. The distribution of TNF- alpha genotypes at -308 [G [rightwards arrow] A] were GG 28.07%, GA 66.67% and AA 5.26% in GC patients and GG 33.19%, GA 55.89% and AA 10.92% in control subjects. The frequencies of alleles G and A were 0.614 and 0.386 in GC patients and 0.611 and 0.389 in control subjects respectively. The study showed no significant difference in the distribution of genotype and allelic frequencies between GC patients and control subject