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.
Highlights
Colorectal cancer (CRC) is the third most common type of cancer in the western world and is responsible for approximately 50,000 deaths per year [1]
It has been suggested that this may be due to carcinogenic polycyclic aromatic hydrocarbons (PAH) and heterocyclic amines (HCA) produced when meat is cooked at high temperatures
A total of 13 studies examined the association between the Cytochrome P450 2C9 (CYP2C9) polymorphism and CRC were included in the current meta-analysis [18,19,20,21,22,23,24,25,26,27,28,29,30]
Summary
Colorectal cancer (CRC) is the third most common type of cancer in the western world and is responsible for approximately 50,000 deaths per year [1]. It has been suggested that this may be due to carcinogenic polycyclic aromatic hydrocarbons (PAH) and heterocyclic amines (HCA) produced when meat is cooked at high temperatures. Data from both in vitro and in vivo studies suggest that exposure to PAH significantly increase colorectal cancer risk [6,7]. A variety of studies have demonstrated that the metabolism of PAH and other procarcinogens through CYP2C9 may well lead to the activation of the carcinogenic compounds [9,10]. CYP2C9 gene may be a good candidate for genetics studies on CRC
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