Peroxisome Proliferator-Activated Receptor-Gamma Pro12Ala Polymorphism Could be a Risk Factor for Gastric Cancer


Background: Due to the strong inhibitory effects of PPARγ gene on the growth of cancer cells, the role ofPro12Ala polymorphism in PPARγ gene has been extensively investigated in cancer recently. However, theresults were inconsistent according to cancer type. The aim of this study was to comprehensively evaluate thePPARγ Pro12Ala polymorphism and gastric cancer susceptibility. Materials and
Methods: Search strategieswere conducted in Pubmed, Medline (Ovid), Chinese biomedical database (CBM), China national knowledgeinfrastructure (CNKI), VIP, and Wanfang database, covering all publications, with the last search up to November01, 2014. The strength of association between PPARγ Pro12Ala polymorphism and gastric cancer risk was assessedby OR with 95%CI.
Results: A total of 546 cases and 827 controls in 5 case-control studies were included in thismeta-analysis. The results indicated that the variant G allele carriers (CG+GG) had a 2.31 times higher risk forgastric cancer when compared with the homozygote CC (odds ratio (OR)=2.31, 95% confidence interval (CI)=1.67-3.21 for CG+GG vs. CC). In the subgroup analysis by ethnicity, significantly elevated risks were both found inAsians (OR=2.56, 95% CI=1.42-4.64) and Caucasians (OR=2.20, 95% CI=1.48-3.25). Similarly, in the subgroupanalysis by H. pylori status, a significantly increased risk was identified in H. pylori (+) populations (OR=3.68,95%CI=2.07-6.52), but not in H. pylori(-) populations (OR=1.17, 95%CI=0.58-2.39).
Conclusions: This pooledanalysis suggested that the PPARγ Pro12Ala polymorphism could be an independent predictive risk factor forgastric cancer especially in H. pylori infected populations in Asians and Caucasians. Nevertheless, prospectivelydesigned cohort studies are needed to further investigate gene-gene and gene-environment interactions to confirmthe combined effects of PPARγ Pro12Ala polymorphisms and H. pylori infection on gastric cancer risk.