Influence of Peroxisome Proliferator-activated Receptor (PPAR)γ Plo12Ala Polymorphism as a Shared Risk Marker for Both Gastric Cancer and Impaired Fasting Glucose (IFG) in Japanese

Department of Gastroenterology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
Digestive Diseases and Sciences (Impact Factor: 2.61). 04/2008; 53(3):614-21. DOI: 10.1007/s10620-007-9944-8
Source: PubMed


Activation of peroxisome proliferator-activated receptor gamma (PPARgamma) has been shown to inhibit the proliferation of gastric cancer cells. A common polymorphism at codon 12 of this gene (Pro12Ala) has been shown to confer protection against diabetes and colorectal cancer. We investigated the influence of PPARgamma gene Plo12Ala polymorphism on the risk of gastric cancer and on the severity of Helicobacter pylori-induced gastritis as well as impaired fasting glucose (IFG) in Japanese. About 215 patients with gastric cancer (GC) and 201 patients without GC enrolled in this study. Plo12Ala polymorphism of PPARgamma was investigated by PCR-RFLP in all of the subjects. The gastritis score of noncancerous antral mucosa was calculated by the updated Sydney system. The diagnosis of IFG was based on repeated evidence of serum fasting glucose (SFG) concentration of greater than or equal to 110 mg/dl. The Plo12Ala genotype of PPARgamma showed a significantly higher frequency in GC patients than in controls (OR = 2.43; 95%CI = 1.04-5.67). In contrast, the Plo12Ala genotype held a lower risk of IFG (OR = 0.33; 95%CI = 0.13-0.83). The same genotype was associated with an increased risk of non-cardiac gastric cancer (OR = 2.39; 95%CI = 1.02-5.65), lower third gastric cancer (OR = 3.56; 95%CI = 1.31-9.71), advanced cancer (OR = 2.93; 95%CI = 1.13-7.58), and Lauren's intestinal cancer (OR = 2.94; 95%CI = 1.13-7.66). Among 151 gastric cancer subjects, the atrophy and metaplasia scores of the antral mucosa adjacent to cancer showed a tendency to be higher in those with the 12Ala allele. Our study suggests that the PPARgamma Pro12Ala polymorphism may be a shared risk marker of both IFG and gastric cancer in Japanese.

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    • "However, recent investigations suggest that antiproliferative effect of ciglitazone and troglitazone in stomach cancer could proceed via a PPARg-independent pathway, as studies examining GW9662, a PPARg antagonist, did not report a growth suppressant effect exerted by either of the two receptor activators (Cheon et al., 2009). Epidemiological studies associate PPARg Pro12Ala polymorphism with gastric cancer and peptic ulcer disease (Tahara et al., 2007; Prasad et al., 2008). It is well documented that PPARg exerts both common and tissue-specific genomic and physiologic effects in the proximal and distal colon (Su et al., 2007) and regulates proliferation and motility of intestinal epithelial cells (Chen et al., 2006). "
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    • "The initial publication reported a 75% risk reduction for diabetes conferred by the Ala allele,12 and it is said that persons with the Ala12 allele have a reduced risk of colorectal cancer,13 prostate cancer,14 endometrial cancer,15 sporadic colorectal adenoma,16 gastric cancer,17 and adenocarcinoma and peptic ulcer disease (PUD).10 "
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    • "It has been reported that PPARγ polymorphism (Pro12Ala) is associated with various disease including diabetes, asthma, endometriosis, polycystic ovary, and colorectal cancer [46–50]. Regarding to gastric disease, this PPARγ polymorphism is associated with not only gastric ulcer but also gastric adenocarcinoma [51–53]. "
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