title: Matrix metalloproteinase3 gene promoter polymorphisms and their haplotypes are associated with gastric cancer risk in eastern Indian population.
abstract: Single nucleotide polymorphisms (SNPs) of matrix metalloproteinase3 (MMP3) promoter in the development and progression of gastric cancer of whole stomach has never been investigated in any population. We conducted a hospital-based case-control study to explore the MMP3 SNPs and their haplotypes with the risk of gastric cancer for the first time in eastern Indian population. A total of 218 gastric cancer patients and 175 healthy controls were genotyped for MMP3-1612 5A/6A (rs3025058) by PCR-RFLP and rechecked 10% by DNA sequencing. MMP3-707 A/G (rs522616) and MMP3-375 C/G (rs617819) were genotyped by DNA sequencing among 209 patients and 154 controls. MMP3-1612 5A6A genotype (P = 0.026, odds ratio (OR) = 1.756, confidence interval (CI) = 1.070-2.883), combined 5A5A and 5A6A genotype (P = 0.015, OR = 1.791, CI = 1.122-2.858) and 5A allele (P = 0.002, OR = 1.75, CI = 1.21-2.53) and; MMP3-707 GG genotype (P = < 0.0001; OR = 9.612; 95% CI = 3.403-27.147), combined GG and AG genotype (P = 0.001, OR = 2.201, CI = 1.385-3.498) and G allele (P = <0.0001, OR = 2.189, CI = 1.582-3.033) conferred significant risk for gastric cancer development. Also, tobacco addicted individuals with combined 5A5A and 5A6A genotype (P = 0.005, OR = 2.952, CI = 1.377-6.327) at -1612 position of MMP3 promoter displayed a higher risk to gastric cancer development. The genotypic combinations of all three MMP3 promoter polymorphisms and their haplotypes with increasing risk allele in a dose-dependent manner showed a potential risk for developing gastric cancer. The analyses suggested that the MMP3-707 G/G and MMP3-1612 5A/6A polymorphisms are potential independent predictors of gastric cancer risk development.
authors: Department of Physiology, Drug Development Diagnostic and Biotechnology Division, Indian Institute of Chemical Biology, Kolkata, India.
authors: Sanjib
authors: S
authors: Dey
authors: Sami
authors: S
authors: Stalin
authors: Arnab
authors: A
authors: Gupta
authors: Debjit
authors: D
authors: Saha
authors: Kousik
authors: K
authors: Kesh
authors: Snehasikta
authors: S
authors: Swarnakar
mesh_terms: D000368:Aged; D001483:Base Sequence; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007194:India; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology
chemical_list: D019278:Matrix Metalloproteinase 3