Peroxisome proliferator-activated receptor (PPAR) gene polymorphisms and colorectal cancer risk among Chinese in Singapore

Department of Community, Occupational and Family Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Carcinogenesis (Impact Factor: 5.33). 10/2006; 27(9):1797-802. DOI: 10.1093/carcin/bgl001
Source: PubMed


Peroxisome proliferator-activated receptor (PPAR) gamma is a ligand-activated nuclear receptor that plays a key role in adipogenesis and adipocyte gene expression, and has recently been linked with possible antineoplastic effects in colonic carcinogenesis. PPARgamma2 and gamma3 are two transcripts arising from the PPARgamma gene through differential promoter usage and alternative splicing. We investigated the associations between PPARgamma2 Pro12Ala and PPARgamma3 C-681G gene polymorphisms and colorectal cancer (CRC) risk in a case-control study nested within the Singapore Chinese Health Study. Genotypes for the PPARgamma2 and PPARgamma3 polymorphisms were determined on 362 incident CRC cases and 1164 cohort controls by direct sequencing and by fluorogenic 5'-nuclease assay. Unconditional logistic regression models were used for statistical analyses. With adjustment for CRC risk factors, subjects with one or two copies of the G allele of the PPARgamma2 Pro12Ala polymorphism showed a statistically significant reduction in risk compared to those with the CC genotype [odds ratio (OR)=0.53, 95% confidence interval (CI)=0.30-0.92]. For the PPARgamma3 C-681G polymorphism, subjects with one or two copies of the C allele showed a reduction in risk compared to those with the GG genotype (OR=0.72, 95% CI=0.51-1.04). When PPARgamma2 and PPARgamma3 genotypes were considered simultaneously, the number of putative low-risk genotypes was significantly associated with reduced risk of CRC in a gene-dose-dependent manner; the OR (95% CI) was 0.72 (0.49-1.07) among subjects possessing one low-risk genotype (either PPARgamma2 or PPARgamma3), and the comparable figure among subjects possessing both low-risk genotypes was 0.19 (0.07-0.51).

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    • "PPARγ polymorphism (Pro12Ala) has been found to be associated with various diseases including type II diabetes, cardiovascular disease, and several types of cancer [48]. Pro12Ala polymorphism lowers the risk of diseases in colorectal cancer and type II diabetes [49]. These results could be partly explained by the etiological link between type II diabetes and colorectal cancer. "
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    ABSTRACT: Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor that is important in many physiological and pathological processes, such as lipid metabolism, insulin sensitivity, inflammation, cell proliferation, and carcinogenesis. Several studies have shown that PPARγ plays an important role in gastric mucosal injury due to Helicobacter pylori (H. pylori). As H. pylori infection is the main etiologic factor in chronic gastritis and gastric cancer, understanding of the potential roles of PPARγ in H. pylori infection may lead to the development of a therapeutic target. In this paper, the authors discuss the current knowledge on the role of PPARγ in H. pylori infection and its related gastric carcinogenesis.
    PPAR Research 08/2012; 2012:687570. DOI:10.1155/2012/687570 · 1.64 Impact Factor
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    ABSTRACT: Colorectal cancer (CRC) etiology involves multiple disease pathways. An important research element for unraveling these carcinogenic pathways to CRC is to gain an understanding of genetic susceptibility to CRC at the population level; single nucleotide polymorphisms (SNPs) are central to this research. Examination of a broad spectrum of SNPs along multiple disease pathways should help our understanding of cancer biology and the carcinogenic process. However, one of the greatest research challenges today will be to implement and interpret studies that utilize SNPs to gain insight into the genetic susceptibility of CRC.
    Current Colorectal Cancer Reports 12/2006; 2(4):200-205. DOI:10.1007/s11888-006-0023-x
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    ABSTRACT: The Pro12Ala polymorphism of PPAR gamma 2 has been shown to influence hypertension and the benefit of longevity in previous studies. We examined whether the polymorphism was related to essential hypertension among long-lived subjects (is greater than 90 years). The Pro12Ala variant was examined using polymerase chain reaction restriction fragment length polymorphism in a population-based sample of 839 long-lived subjects (mean 94 years SD 4 years, aged 90-108 years). The genotype frequencies of the Pro12Ala polymorphism were 0.2% Ala12Ala, 9.4% Pro12Ala and 90.4% Pro12Pro in all participants. The frequency of the Ala12 allele was 3.45% in the hypertension group and 6.92% among the normotension group (P=0.001). Moreover, in the total study population, Ala12 allele carriers had lower levels of triglycerides (1.03+/-0.5 mmol/L (means+/-SD) vs. 1.25+/-0.61 mmol/L; P<0.001). In conclusion, these results suggest that the Pro12Ala polymorphism of the PPAR gamma 2 gene is associated with hypertension and triglycerides levels in Chinese nonagenarians/centenarians.
    Experimental gerontology 09/2008; 43(12):1108-13. DOI:10.1016/j.exger.2008.08.046 · 3.49 Impact Factor
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