Gastric cancer 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 the outcome and severity of the disease. Transforming growth factor (TGF-β) signaling pathway plays an important role in the genesis and progression of tumors through regulating cell proliferation and differentiation. A hospital-based case-control study was conducted to investigate whether TGF-β1 -509 C/T polymorphism can modify the risk of gastric cancer. Seventy endoscopically and histopathologically confirmed gastric cancer patients and 100 age and sex-matched healthy controls were enrolled in the case-control study. TGF-β1 -509 C/T gene polymorphism was carried out by amplification refractory mutation system polymerase chain reaction (ARMS-PCR) method followed by agarose gel electrophoresis. Statistical analysis was applied to test for the significance of the results. The distribution of TGF-β1 genotypes at -509 C/T were CC 37.14%, CT 50%, and TT 12.86% in gastric cancer patients and CC 52%, CT 42%, and TT 6% in control subjects. The allelic frequencies of C and T were 0.621 and 0.379 in gastric cancer patients and 0.73 and 0.27 in control subjects, respectively. Our study imply that T allele of TGF-β1 -509 C/T genotypes may be a risk factor of genetic susceptibility to gastric cancer in south Indian population.

BackgroundGastric cancer (GC) is the fifth most common malignancy and remains a considerable public health burden worldwide. Genetic variations in genes encoding cytokines and their receptors influence the intensity of the Helicobacter pylori associated inflammatory response, which may contribute to individual differences in the outcome and severity of the disease. Interleukin4 is a typical pleiotropic T helper 2 (Th2) cytokine and is a critical mediator of Th1/Th2 balance. It is involved in the regulation of inflammation-mediated carcinogenesis in human organs, including gastric cancer.ObjectiveThe present retrospective case control study was undertaken to evaluate the association of IL4 intron 3 VNTR polymorphism with the susceptibility to GC in a south Indian population from Telangana state.Materials and MethodsA total of 182 patients with diagnosed GC and 326 randomly selected healthy controls were enrolled in the present study. Genomic DNA was extracted from peripheral leukocytes and genotyping was determined by PCR-based assay. Association between genotypes and gastric cancer was examined by unconditional logistic regression analysis.ResultThe variant 3R/2R and 2R/2R genotypes of IL4 exon3 VNTR polymorphism had about 1.9 fold and 3fold increased GC risk, respectively, when compared with 3R/3R genotype [3R/2R vs. 3R/3R: adjusted odds ratio (AOR) = 1.90, 95% confidence interval (CI) = 1.23–2.95 P = 0.004 and 2R/2R vs. 3R/3R: AOR (95%CI) = 2.96 (1.29–6.82), P = 0.011]. Furthermore, a significant increased risk of GC was found for the 2R allele carriers (3R/2R + 2R/2R) compared with the 3R/3R genotype (AOR (95%CI) = 2.04 (1.35–3.10), P = <0.000). The IL4 2R allele frequency was 0.28 among the GC group and 0.18 among the controls, and the difference was statistically significant (P = <0.000).ConclusionThe present study revealed an association of 2R allele and 2R carrier genotypes in the etiopathogenesis of GC in south Indian population.

Matrix metalloproteinase-9 (gelatinase B) plays a key role in cancer invasion and metastasis by degrading the extracellular matrix and basement membrane barriers. A cytosine (C) > thymidine (T) single nucleotide polymorphism (SNP) at position -1562 in the MMP-9 promoter is reported to influence the expression of the gene. Genotyping of MMP-9 -1562 C→T promoter polymorphism in 140 gastric cancer patients and 132 healthy control subjects was carried out in order to evaluate its association with progression and development of gastric cancer. The SNP was genotyped by tetra-primer amplification refractory mutation system-polymerase chain reaction followed by agarose gel electrophoresis. Statistical methods were adopted to test for the significance of the results. Risk factor profile of the patients revealed age above 50 years, smoking, alcoholism as the factors associated with the disease. The distribution of genotype frequencies in gastric cancer patients were 28.7 % of CC, 45.5 % of CT and 25.7 % of TT, whereas in control subjects 31.8 % of CC, 53.03 % of CT and 15.15 % of TT, respectively. The allelic frequencies were 51.51 % of C and 48.48 % of T in patient group and 58.33 % of C and 41.66 % of T in controls respectively. The present study shows the possible association of epidemiological risk factors with gastric cancer. There is an increased frequency of T allele in the disease compared to control subjects. However, there is no association of the MMP-9 -1562 C→T promoter polymorphism in the development of gastric cancer.