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Association of MMP7-181A-G Promoter Polymorphism with Gastric Cancer Risk

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Title Association of MMP7-181A-G Promoter Polymorphism with Gastric Cancer Risk
 
Creator Kesh, Kousik
Subramanian, Lakshmi
Ghosh, Nillu
Gupta, Vinayak Gupta
Gupta, Arnab
Bhattacharya, Samir
Mahapatra, Nitish R.
Swarnakar, Snehasikta
 
Subject Drug Development/Diagnostics & Biotechnology
 
Description Elevated expression of matrix metalloproteinase7 (MMP7)
has been demonstrated to play a pivotal role in cancer invasion.The�181A3G(rs11568818) polymorphism in theMMP7promoter modulates gene expression and possibly affects cancer progression. Here, we evaluated the impact of�181A3G polymorphism on MMP7 promoter activity and its association with gastric cancer risk in eastern Indian case-control cohorts (n �520). The GG genotype as compared with the AA genotype was predisposed (p � 0.02; odds ratio � 1.9, 95% confidence interval1.1–3.3) to gastric cancer risk. Stratification analysis showed that tobacco addiction enhanced gastric cancer risk in GG subjects when compared with AA subjects (p � 0.03, odds ratio � 2.46, and 95% confidence interval � 1.07–5.68). Metaanalysis
revealed that tobacco enhanced the risk for cancer more
markedly in AG and GG carriers. Activity and expression of
MMP7 were significantly higher in GG than in AA carriers. In
support, MMP7 promoter-reporter assays showed greater transcriptional activity toward A to G transition under basal/nicotine- induced/cAMP-response element-binding protein (CREB) overexpressed conditions in gastric adenocarcinoma cells. Moreover, nicotine (a major component of tobacco) treatment significantly up-regulated MMP7 expression due to enhanced CREB phosphorylation followed by its nuclear translocation in gastric adenocarcinoma cells. Furthermore, chromatin immunoprecipitation experiments revealed higher binding of phosphorylated CREB with the �181G than the �181A allele. Altogether, specific binding of phosphorylated CREB to the G allele-carrying promoter enhances MMP7 gene expression that is further augmented by nicotine due to increased CREB phosphorylation and thereby increases the risk for gastric cancer.
 
Publisher American Society for Biochemistry and Molecular Biology
 
Date 2015
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2222/1/JOURNAL_OF_BIOLOGICAL_CHEMISTRY__Volume_290___Issue_23___Pages_14391%2D14406_;2015[5].pdf
Kesh, Kousik and Subramanian, Lakshmi and Ghosh, Nillu and Gupta, Vinayak Gupta and Gupta, Arnab and Bhattacharya, Samir and Mahapatra, Nitish R. and Swarnakar, Snehasikta (2015) Association of MMP7-181A-G Promoter Polymorphism with Gastric Cancer Risk. The Journal of Biological Chemistry, 290 (23). pp. 14391-14406.
 
Relation http://dx.doi.org/10.1074/jbc.M114.630129
http://www.eprints.iicb.res.in/2222/