CYP2W1 Variant Alleles in Caucasians and Association of the CYP2W1 G541A (Ala181Thr) Polymorphism with Increased Colorectal Cancer Risk

Abstract

Aims: To detect differences in the frequency of the known nonsynonymous CYP2W1 polymorphisms between colorectal cancer patients and healthy subjects. Materials & methods: The study group consisted of 150 colorectal patients and 263 controls. The presence of five nonsynonymous CYP2W1 polymorphisms was analyzed by novel amplification-restriction methods. Results: Two nonsynonymous SNPs causing the amino acid substitutions Val432Ile and Gln482His were monomorphic in the population study. Two nonsynonymous SNPs previously unknown in Caucasians, 1463T (rs3808348) and 173C (no rs number assigned), were detected in the population study, although these were not associated with colorectal cancer risk. Regarding the 541G/A polymorphism (rs3735684), the 541G allele (odds ratio: 2.2; 95% CI: 1.2–4.1) and the 541GG genotype (odds ratio: 2.06; 95% CI: 1.1–3.9) were associated with increased colorectal cancer risk in the population studied. Conversely, the 173C-541A-1463C haplotype (odds ratio: 0.46; 95% CI: 0.2–0.9) showed a protective odds ratio value. Conclusion:CYP2W1 variant alleles are common among Caucasian individuals and, of these, the CYP2W1 G541A (Ala181Thr) polymorphism is associated with increased colorectal cancer risk.

KEYWORDS::

• colorectal cancer
• CYP2W1
• pharmacogenetics
• polymorphisms
• SNP

Acknowledgements

We are thankful to Ms Mercedes Jimenez for her excellent technical assistance.

Financial & competing interests disclosure

This work has been supported in part by grants PRI08A008 and PRI07A006 from Junta de Extremadura, Consejeria de Economia, Comercio e Innovacion, Merida, Spain and PS09/00943 and RD07/0064/0016 from Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Madrid, Spain. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work has been supported in part by grants PRI08A008 and PRI07A006 from Junta de Extremadura, Consejeria de Economia, Comercio e Innovacion, Merida, Spain and PS09/00943 and RD07/0064/0016 from Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Madrid, Spain. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.