title: Matrix metalloproteinase-1 (MMP-1) Promoter polymorphisms are well linked with lower stomach tumor formation in eastern Indian population.
abstract: Expression of matrix metalloproteinase-1 (MMP-1), an interstitial collagenase, plays a major role in cellular invasion during development of gastric cancer, a leading cause of death worldwide. A single-nucleotide polymorphism (SNP) -1607 1G/2G site of the MMP-1 gene promoter has been reported to alter transcription level. While the importance's of other SNPs in the MMP-1 promoter have not yet been studied in gastric cancer, our aim was to investigate MMP-1 gene promoter polymorphisms and gastric cancer susceptibility in eastern Indian population. A total of 145 gastric cancer patients and 145 healthy controls were genotyped for MMP-1 -1607 1G/2G (rs1799750) by PCR-restriction fragment length polymorphism (RFLP), while MMP-1 -519 A/G (rs1144393), MMP-1 -422 T/A (rs475007), MMP-1 -340 T/C (rs514921) and MMP-1 -320 T/C (rs494379) were genotyped by DNA sequencing. A positive association was found with MMP-1 -422 T/A SNP that showed significant risk for regional lymph node metastasis (P = 0.021, Odd's ratio (OR) = 3.044, Confidence intervals (CI) = 1.187-7.807). In addition, we found a significant association with lower stomach tumor formation among gastric cancer patients for three adjacent polymorphisms near the transcriptional start sites of [MMP-1 -422 T/A (P = 0.043, OR = 2.182, CI = 1.03-4.643), MMP-1 -340 T/C (P = 0.075, OR = 1.97, CI = 0.94-4.158) and MMP-1 -320 T/C (P = 0.034, OR = 2.224, CI = 1.064-40731)]. MMP-1 level in patients' serum was correlated with MMP-1 promoter haplotypes conferring these three SNPs to evaluate the functional importance of these polymorphisms in lower stomach tumor formation and significant correlation was observed. Furthermore, MMP-1 -519 A/G polymorphism displayed poor cellular differentiation (P = 0.024, OR = 3.8, CI = 1.69-8.56) attributing a higher risk of cancer progression. In conclusion, MMP-1 proximal promoter SNPs are associated with the risk of lower stomach tumor formation and node metastasis in eastern Indian population.
authors: Drug Development Diagnostic and Biotechnology Division, Indian Institute of Chemical Biology, Kolkata, India.
authors: Sanjib
authors: S
authors: Dey
authors: Drug Development Diagnostic and Biotechnology Division, Indian Institute of Chemical Biology, Kolkata, India.
authors: Nillu
authors: N
authors: Ghosh
authors: Drug Development Diagnostic and Biotechnology Division, Indian Institute of Chemical Biology, Kolkata, India.
authors: Debjit
authors: D
authors: Saha
authors: Drug Development Diagnostic and Biotechnology Division, Indian Institute of Chemical Biology, Kolkata, India.
authors: Kousik
authors: K
authors: Kesh
authors: Saroj Gupta Cancer Center and Research Institute, Kolkata, India.
authors: Arnab
authors: A
authors: Gupta
authors: Drug Development Diagnostic and Biotechnology Division, Indian Institute of Chemical Biology, Kolkata, India.
authors: Snehasikta
authors: S
authors: Swarnakar
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006239:Haplotypes; D006801:Humans; D007194:India / Q000453:epidemiology; D015810:Linkage Disequilibrium; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology
chemical_list: D020781:Matrix Metalloproteinase 1