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

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. PPAR gamma 2 and gamma 3 are two transcripts arising from the PPAR gamma gene through differential promoter usage and alternative splicing. We investigated the associations between PPAR gamma 2 Pro12Ala and PPAR gamma 3 C-681G gene polymorphisms and colorectal cancer (CRC) risk in a case-control study nested within the Singapore Chinese Health Study. Genotypes for the PPAR gamma 2 and PPAR gamma 3 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 PPAR gamma 2 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 PPAR gamma 3 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 PPAR gamma 2 and PPAR gamma 3 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 PPAR gamma 2 or PPAR gamma 3), and the comparable figure among subjects possessing both low-risk genotypes was 0.19 (0.07-0.51).