Abstract
Due to the strong inhibitory effects of PPARγ gene on the growth of cancer cells, the role of Pro12Ala polymorphism in PPARγ gene has been extensively investigated in cancer recently. However, the results were inconsistent according to cancer type. The aim of this study was to comprehensively evaluate the PPARγ Pro12Ala polymorphism and gastric cancer susceptibility. Search strategies were conducted in Pubmed, Medline (Ovid), Chinese biomedical database (CBM), China national knowledge infrastructure (CNKI), VIP, and Wanfang database, covering all publications, with the last search up to November 01, 2014. The strength of association between PPARγ Pro12Ala polymorphism and gastric cancer risk was assessed by OR with 95%CI. A total of 546 cases and 827 controls in 5 case-control studies were included in this meta-analysis. The results indicated that the variant G allele carriers (CG+GG) had a 2.31 times higher risk for gastric 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 in Asians (OR=2.56, 95% CI=1.42-4.64) and Caucasians (OR=2.20, 95% CI=1.48-3.25). Similarly, in the subgroup analysis 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). This pooled analysis suggested that the PPARγ Pro12Ala polymorphism could be an independent predictive risk factor for gastric cancer especially in H. pylori infected populations in Asians and Caucasians. Nevertheless, prospectively designed cohort studies are needed to further investigate gene-gene and gene-environment interactions to confirm the combined effects of PPARγ Pro12Ala polymorphisms and H. pylori infection on gastric cancer risk.
Highlights
The incidence and mortality of gastric cancer have decreased dramatically over the past several decades
When activated by specific ligand, Peroxisome proliferator-activated receptor γ (PPARγ) forms heterodimer with retinoid X receptor (RXR), the PPARγ/RXR heterodimer binds to specific DNA response elements called peroxisome proliferator response elements (PPREs), regulates the transcription of PPARresponsive genes(Konturek et al, 2003; Nolte et al, 1998) including lipid metabolism, inflammation, insulin sensitization, cell proliferation and carcinogenesis
It was reported that activation of PPARγ inhibits the proliferation of gastric cancer cells through induction of cell cycle arrest and apoptosis (Sato et al, 2000; Grommes et al, 2004; Leung et al, 2004; Theocharis et al, 2004)
Summary
The incidence and mortality of gastric cancer have decreased dramatically over the past several decades. Most of H. pylori infected individuals remain asymptomatic and only fewer than 0.5% of infected individuals develop gastric cancer, even though expose in the same environment (Shi et al, 2014). This indicates that genetic differences, such as variants and single nucleotide polymorphisms (SNPs), may play a crucial role in gastric carcinogenesis. Conclusions: This pooled analysis suggested that the PPARγ Pro12Ala polymorphism could be an independent predictive risk factor for gastric cancer especially in H. pylori infected populations in Asians and Caucasians. Prospectively designed cohort studies are needed to further investigate gene-gene and gene-environment interactions to confirm the combined effects of PPARγ Pro12Ala polymorphisms and H. pylori infection on gastric cancer risk
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Asian Pacific journal of cancer prevention : APJCP
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
