Quantitative assessment of the effect of cytochrome P450 2C9 gene polymorphism and colorectal cancer

PLoS One. 2013;8(4):e60607. doi: 10.1371/journal.pone.0060607. Epub 2013 Apr 5.

Abstract

CYP2C9 enzyme activity is involved in the metabolism of substances related to colorectal cancer (CRC), and it is functionally linked to a genetic polymorphism. Two allelic variants of the CYP2C9 gene, namely CYP2C9*2 and CYP2C9*3, differ from wild-type CYP2C9*1 by single amino acid substitutions. These mutated alleles encode enzymes with altered properties that are associated with impaired metabolism. In the past decade, a number of case-control studies have been carried out to investigate the relationship between the CYP2C9 polymorphism and CRC susceptibility, but the results were conflicting. To investigate this inconsistency, we performed a meta-analysis of 13 studies involving a total of 20,879 subjects for CYP2C9*2 and *3 polymorphisms to evaluate the effect of CYP2C9 on genetic susceptibility for CRC. Overall, the summary odds ratio of CRC was 0.94 (95%CI: 0.87-1.03, P = 0.18) and 1.00 (95%CI: 0.86-1.16, P = 0.99) for CYP2C9 *2 and *3 carriers, respectively. No significant results were observed in heterozygous and homozygous when compared with wild genotype for these polymorphisms. In the stratified analyses according to ethnicity, sample size, diagnostic criterion, HWE status and sex, no evidence of any gene-disease association was obtained. Our result suggest that the *2, *3 polymorphisms of CYP2C9 gene are not associated with CRC susceptibility.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Colorectal Neoplasms / enzymology*
  • Colorectal Neoplasms / genetics*
  • Cytochrome P-450 CYP2C9
  • Female
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Male
  • Polymorphism, Single Nucleotide*

Substances

  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases

Grants and funding

This work was supported by China Postdoctoral Science Foundation Funded Project (20100480542, 201104227), National Natural Science Foundation of China (81201535), Nature Science Foundation of Shanghai (12ZR1436000), Youth Innovation Promotion Association and the Knowledge Innovation Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.