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

Abstract

Peroxisome proliferator-activated receptor (PPAR) γ 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. PPARγ2 and γ3 are two transcripts arising from the PPARγ gene through differential promoter usage and alternative splicing. We investigated the associations between PPARγ2 Pro12Ala and PPARγ3 C-681G gene polymorphisms and colorectal cancer (CRC) risk in a case-control study nested within the Singapore Chinese Health Study. Genotypes for the PPARγ2 and PPARγ3 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 PPARγ2 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 PPARγ3 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 PPARγ2 and PPARγ3 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 PPARγ2 or PPARγ3), and the comparable figure among subjects possessing both low-risk genotypes was 0.19 (0.07-0.51). © 2006 Oxford University Press.