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

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

Association of interleukin-10 promoter polymorphism [-1082 G/A] and gastric cancer in Andhra Pradesh population of South India

Gastric Cancer [GC] is one of the most commonly diagnosed malignancies. Genetic variation in genes encoding cytokines and their receptors, determine the intensity of the inflammatory response, which may contribute to individual differences in the outcome and severity of the disease. Interleukin-10 [IL-10] is a multifunctional cytokine with both immunosuppressive and antiangiogenic functions. Polymorphisms in the IL-10 gene promoter genetically determine inter-individual differences in IL-10 production. In the present study, we investigated the association between the IL-10 -1082 G/A polymorphism and the susceptibility to gastric cancer in a South Indian population from Andhra Pradesh. We genotyped 100 patients diagnosed with gastric cancer and 132 healthy control subjects for -1082G/A single nucleotide polymorphism by Amplification Refractory Mutation System-Polymerase Chain Reaction [ARMS-PCR] method followed by agarose gel electrophoresis. The distribution of IL-10 genotypes at -1082 G/A were GG 18%, GA 35% and AA 47% in gastric cancer patients and GG 31.82%, GA 37.88% and AA 30.3% in control subjects. The allelic frequencies of G and A were 0.355 and 0.645 in GC patients and 0.508 and 0.492 in control subjects respectively. The IL-10 -1082 A allele was associated with risk of gastric cancer [OR=1.873, 95%CI-1.285-2.73and P= 0.001048**]. Our study indicates that allele A of IL-10-1082 G/A polymorphism may be considered as one of the important risk factor in the etiology of gastric cancer