Carcinogenesis Advance Access originally published online on March 2, 2006
Carcinogenesis 2006 27(9):1797-1802; doi:10.1093/carcin/bgl001
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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
1 The Cancer Center, University of Minnesota MN, USA
2 USC/Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California Los Angeles, CA, USA
*To whom correspondence should be addressed at: Department of Community, Occupational and Family Medicine, Yong Loo Lin School of Medicine, National University of Singapore, MD3, 16 Medical Drive, Singapore 117597. Tel: +65 6874 4975; Fax: +65 6779 1489; Email: cofkwp{at}nus.edu.sg
Peroxisome proliferator-activated receptor (PPAR) 
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. PPAR2 and 3 are two transcripts arising from the PPAR gene through differential promoter usage and alternative splicing. We investigated the associations between PPAR2 Pro12Ala and PPAR3 C-681G gene polymorphisms and colorectal cancer (CRC) risk in a case–control study nested within the Singapore Chinese Health Study. Genotypes for the PPAR2 and PPAR3 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 PPAR2 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 PPAR3 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 PPAR2 and PPAR3 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 PPAR2 or PPAR3), and the comparable figure among subjects possessing both low-risk genotypes was 0.19 (0.07–0.51).