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Carcinogenesis Advance Access published online on March 2, 2006
Carcinogenesis, doi:10.1093/carcin/bgl001
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
Received November 23, 2005
Revised January 31, 2006
Accepted February 21, 2006

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

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

Woon-Puay Koh 1 *, Jian-Min Yuan 2, David Van Den Berg 3, Sue A. Ingles 3, and Mimi C. Yu 2

1 Department of Community, Occupational and Family Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
2 The Cancer Center, University of Minnesota, Minneapolis, USA
3 USC/Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA

* To whom correspondence should be addressed.
Woon-Puay Koh, E-mail: cofkwp{at}nus.edu.sg


  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. PPAR{gamma}2 and PPAR{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 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 colorectal cancer 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 colorectal cancer 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 colorectal cancer 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).

Keywords: peroxisome proliferator-activated receptor (PPAR) {gamma}; colorectal cancer; gene polymorphism.
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