Variant alleles of the CYP1B1 gene are associated with colorectal cancer susceptibility

BMC Cancer

Research Article

Cezary Cybulski¹  Janina Suchy¹  Elżbieta Kowalska¹  Joanna Trubicka¹  Pablo Serrano-Fernandez¹  Tomasz Byrski¹  Jacek Gronwald¹  Tomasz Huzarski¹  Bohdan Górski¹  Bartłomiej Masojć¹  Ewa Grabowska-Kłujszo¹  Grzegorz Kurzawski¹  Elżbieta Złowocka¹  Jan Lubinski¹  Zbigniew Banaszkiewicz²  Rodney J Scott³  Józef Kładny⁴  Rafał Wiśniowski⁵ 

[1] Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland;Department of Surgery, Medical Academy, Bydgoszcz, Poland;Discipline of Medical Genetics, School of Biomedical Sciences, Faculty of Health, University of Newcastle and the Hunter Medical Research Institute, Newcastle, NSW, Australia;Children's Cancer Research Group, Hunter Medical Research Institute, John Hunter Hospital, Lookout Road, 2305, New Lambton, NSW, Australia;III Department of Surgery, Pomeranian Academy of Medicine, Szczecin, Poland;Regional Oncology Hospital, Bielsko Biała, Poland;

关键词: Colorectal Cancer;    Colorectal Cancer Risk;    CYP1B1 Gene;    Genetic Risk Assessment;    Homozygote Carrier;   

DOI  :  10.1186/1471-2407-10-420

 received in 2009-08-29, accepted in 2010-08-11,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundCYP1B1 is a P450 enzyme which is involved in the activation of pro-carcinogens to carcinogens as well as sex hormone metabolism. Because differences in the activity of the enzyme have been correlated with variant alleles of single nucleotide polymorphisms (SNPs), it represents an attractive candidate gene for studies into colorectal cancer susceptibility.MethodsWe genotyped 597 cancer patients and 597controls for three CYP1B1 SNPs, which have previously been shown to be associated with altered enzymatic activity. Using the three SNPs, eight different haplotypes were constructed. The haplotype frequencies were estimated in cases and controls and then compared. The odds ratio for each tumour type, associated with each haplotype was estimated, with reference to the most common haplotype observed in the controls.ResultsThe three SNPs rs10012, rs1056827 and rs1056836 alone did not provide any significant evidence of association with colorectal cancer risk. Haplotypes of rs1056827 and rs10012 or rs1056827 and rs1056836 revealed an association with colorectal cancer which was significantly stronger in the homozygous carriers. One haplotype was under represented in the colorectal cancer patient group compared to the control population suggesting a protective effect.ConclusionGenetic variants within the CYP1B1 that are associated with altered function appear to influence susceptibility to a colorectal cancer in Poland. Three haplotypes were associated with altered cancer risk; one conferred protection and two were associated with an increased risk of disease. These observations should be confirmed in other populations.

【 授权许可】

Unknown   
© Trubicka et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.