Matrix metalloproteinase-1 (MMP-1) Promoter polymorphisms are well linked with lower stomach tumor formation in eastern Indian population

PLoS One. 2014 Feb 5;9(2):e88040. doi: 10.1371/journal.pone.0088040. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Asian People / genetics
  • Case-Control Studies
  • Female
  • Gastric Mucosa / metabolism
  • Haplotypes
  • Humans
  • India / epidemiology
  • Linkage Disequilibrium
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / pathology
  • Male
  • Matrix Metalloproteinase 1 / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic
  • Stomach / pathology
  • Stomach Neoplasms / epidemiology
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology

Substances

  • Matrix Metalloproteinase 1

Grants and funding

Sanjib Dey was recipient of Senior Research Fellowship from Indian Council of Medical Research (ICMR), India. NG and KK are recipient of Senior Research Fellowship from Council of Scientific and Industrial Research (CSIR). The work was supported by grant IAP001 of Council of Scientific and Industrial Research (CSIR), India, NBA07 of Department of Biotechnology (DBT), India. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.