Article

Peroxisome proliferator-activated receptor (PPAR) gamma 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: 5.27). 10/2006; 27(9):1797-802. 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).

0 Bookmarks
 · 
70 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: It is widely accepted that chronic inflammation plays a role in the etiology of colorectal cancer. Using a two-stage design, we examined the associations between colorectal cancer and common variation in 37 key genes in the inflammation and innate immunity pathways. Methods: In the discovery stage, 2,322 discordant sibships (2,535 cases, 3,915 sibling controls) from the Colorectal Cancer Family Registry were genotyped for over 600 tagSNPs and 99 SNPs were selected for further examination based on strength of association. In the second stage, 351 SNPs tagging gene regions covered by the 99 SNPs were tested in 4,783 Multiethnic Cohort subjects (2,153 cases, 2,630 controls). Results: The association between rs9858822 in the PPARG gene and colorectal cancer was statistically significant at the end of the second stage (odds ratio per allele = 1.36, Bonferroni-adjusted P = 0.045), based on the "effective" number of markers in Stage 2 (n = 306). The risk allele C was common (frequency 0.3) in African Americans but rare (frequency < 0.03) in whites, Japanese Americans, Latinos and Native Hawaiians. No statistically significant heterogeneity of effects across race/ethnicity, BMI levels, regular aspirin use or pack-years of smoking was detected for this SNP. Suggestive associations were also observed for several SNPs in close vicinity to rs9858822. Conclusions: Our results provide new evidence of association between PPARG variants and colorectal cancer risk. Impact: Further replication in independent samples is warranted.
    Cancer Epidemiology Biomarkers & Prevention 09/2013; 22(11). DOI:10.1158/1055-9965.EPI-13-0694 · 4.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: The aim of this study was to determine whether six genetic polymorphisms confer susceptibility to colorectal cancer (CRC). Methods: A systematic search for candidate genes of CRC was performed among several online databases, including PubMed, Embase, Web of Science, the Cochrane Library, CNKI, and Wanfang online libraries. After a comprehensive filtering procedure, we harvested five genes, including MGMT (rs12917 and rs2308321), ADH1B (rs1229984), SOD2 (rs4880), XPC (rs2228001), and PPARG (rs1801282). Using the REVMAN and Stata software, six meta-analyses were conducted for associations between CRC and the just-mentioned genetic variants. Results: A total of 34 comparative studies among 17,289 cases and 54,927 controls were involved in our meta-analyses. Significant association was found between ADH1B rs1229984 polymorphism and CRC (p=0.03, odds ratio [OR]=1.18, 95% confidence interval [CI]=1.01-1.36). We also found significant association between PPARG rs1801282 polymorphism and CRC (p=0.004, OR=1.498, 95% CI=1.139-1.970), and this significant association is specific in Caucasians (p=0.004, OR=1.603, 95% CI=1.165-2.205). Conclusions: The current meta-analysis has established that ADH1B (rs1229984) and PPARG (rs1801282) are two risk variants of CRC.
    Genetic Testing and Molecular Biomarkers 02/2014; DOI:10.1089/gtmb.2013.0425 · 1.44 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The peroxisome proliferator-activated receptor (PPAR) family is an important group of transcription factors that regulates immune surveillance, cell proliferation, fatty acid regulation, and angiogenesis—functions which have all been implicated in the pathogenesis of bladder cancer. One particular subtype, PPARγ, is expressed at higher levels in bladder cancer specimens than in benign urothelium, and is an attractive molecular target for the development of novel treatment strategies for bladder cancer. In this review, we summarize the data available regarding relevance of PPARγ in bladder cancer and discuss the potential value of PPAR-targeted treatment of bladder cancer.
    Urologic Oncology 11/2009; 27(6):585-591. DOI:10.1016/j.urolonc.2008.11.002 · 3.36 Impact Factor

Preview

Download
0 Downloads