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Matrix Metalloproteinase-1 (MMP-1) Promoter Polymorphisms are Well Linked with Lower Stomach Tumor Formation in Eastern Indian Population

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Title Matrix Metalloproteinase-1 (MMP-1) Promoter Polymorphisms are Well Linked with Lower Stomach Tumor Formation in Eastern Indian Population
 
Creator Dey, Sanjib
Ghosh, Nillu
Saha, Debjit
Kesh, Kousik
Gupta, Arnab
Swarnakar, Snehasikta
 
Subject Drug Development/Diagnostics & Biotechnology
 
Description 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) 21607 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 21607 1G/2G (rs1799750) by PCR-restriction fragment length polymorphism (RFLP), while MMP-1 2519 A/G (rs1144393), MMP-1 2422 T/A (rs475007), MMP-1 2340 T/C (rs514921) and MMP-1 2320 T/C (rs494379) were genotyped by DNA sequencing. A positive association was found with MMP-1 2422 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 2422 T/A (P = 0.043, OR = 2.182, CI = 1.03– 4.643), MMP-1 2340 T/C (P = 0.075, OR = 1.97, CI = 0.94–4.158) and MMP-1 2320 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 2519 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.
 
Date 2014
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2030/1/PLOS_ONE___9__(_2_)Article_Number_e880402014(7).pdf
Dey, Sanjib and Ghosh, Nillu and Saha, Debjit and Kesh, Kousik and Gupta, Arnab and Swarnakar, Snehasikta (2014) Matrix Metalloproteinase-1 (MMP-1) Promoter Polymorphisms are Well Linked with Lower Stomach Tumor Formation in Eastern Indian Population. PLOS ONE, 9 (2).
 
Relation http://www.eprints.iicb.res.in/2030/