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

ArticleinCarcinogenesis 27(9):1797-802 · October 2006with7 Reads
DOI: 10.1093/carcin/bgl001 · Source: PubMed
Abstract
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).
    • "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. "
    [Show abstract] [Hide abstract] 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.
    Full-text · Article · Aug 2012
    • "Ten functional single nucleotide polymorphisms (SNPs) in three genes, LEP, LEPR and PPARg were selected from previously reported studies (Paynter et al., 2004; Koh et al., 2006; Snoussi et al., 2006; Vogel et al., 2006). The multiplex PCR and extended primers were designed using MassARRAY Assay Design software version 3.0 (Sequenom, CA, USA). "
    [Show abstract] [Hide abstract] ABSTRACT: STUDY QUESTION Is there any effect of genetic polymorphisms in adiposity-related genes on the timing of menarche and menopause and the total duration of menstruation among Korean women? SUMMARY ANSWER Our results suggest that the adiposity-related genes LEP, LEPR and PPARγ may play a role in the onset and cessation of menstruation, and the total duration of menstruation. WHAT IS KNOWN AND WHAT THIS PAPER ADDS Previous candidate-gene approaches have mainly presented the results for genes related to the estrogen metabolism pathway. Most genes of interest that participate in steroid-hormone metabolism, such as estrogen receptor α and estrogen receptor β, have been associated with age at menarche and menopause. This study shows the possibility that adiposity-related genes also influence the duration of menstruation. PARTICIPANTS AND SETTING We recruited 400 breast cancer patients and 452 healthy participants from a case–control study at the Center for Breast Cancer, National Cancer Center in Korea. Ten single nucleotide polymorphisms (SNPs) in the leptin (LEP), leptin receptor (LEPR) and peroxisome proliferator-activated receptor gamma (PPARγ) genes were investigated to evaluate their possible effects on menstruation. Associations between SNPs and age at menarche, age at menopause and duration of menstruation were evaluated. MAIN RESULTS Four SNPs (rs2167270 of LEP, rs7602 of LEPR and rs4684846 and rs3856806 of PPARγ) were associated with late menarche (≥17-year-old). Four SNPs (rs2167270 of LEP and rs1801282, rs2120825, and rs3856806 of PPARγ) were associated with early menopause (
    Article · Apr 2012
    • "Former studies, which investigated the impact of a polymorphic expression of PPARγ on diseases characterized by proinflammatory processes, focused specifically only on the analysis of the two commonly occurring NR1C3 SNPs rs1801282 and/or rs3856806. Several investigations showed that these NR1C3 gene variants are putatively associated with a moderately higher risk for the development of lifestyleassociated diseases (e.g., metabolic syndrome, coronary artery disease, and type 2 diabetes) or for colorectal cancer23242526272829. However, these findings were only partly supported in subsequent meta-analyses303132. "
    [Show abstract] [Hide abstract] ABSTRACT: PPARγ is a nuclear receptor that regulates numerous pathways including cytokine expression and immune responses and plays an important role in controlling colon inflammation. We aimed at determining the occurring PPARγ SNPs, at predicting the haplotypes, and at determining the frequency outcome in inflammatory bowel disease (IBD) patients in comparison with healthy controls. We determined genetic variants in the coding exons and flanking intronic sequences of the NR1C3 gene in 284 IBD patients and 194 controls and predicted NR1C3 haplotypes via bioinformatic analysis. We investigated whether certain NR1C3 variants are associated with susceptibility to IBD or its disease course. None of the detected 22 NR1C3 variants were associated with IBD. Two variants with allelic frequencies over 1% were included in haplotype/diplotype analyses. None of the NR3C1 haplotypes showed association with IBD development or disease course. We conclude that NR1C3 haplotypes are not related to IBD susceptibility or IBD disease activity.
    Full-text · Article · Feb 2012
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