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Cytochrome P1B1 gene (CYP1B1) polymorphisms and ovarian cancer risk:a meta-analysis

Gajjar, Ketan and Owens, Gemma and Sperrin, Matthew and Martin-Hirsch, Pierre L and Martin, Francis L (2012) Cytochrome P1B1 gene (CYP1B1) polymorphisms and ovarian cancer risk:a meta-analysis. Toxicology, 302 (2-3). pp. 157-162.

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Abstract

CYP1B1 is a key P450 enzyme involved in the metabolism of exogenous and endogenous substrates and plays a key role in hormone-induced carcinogenesis. Risk factors for ovarian cancer are related to hormonal exposure and reproduction, and polymorphisms within genes involved in metabolism of oestrogen and certain xenobiotics may influence the risk of developing ovarian cancer. Current meta-analysis evaluated four CYP1B1 polymorphisms (Leu432Val, Arg48Gly, Ala119Ser and Asn453Ser) for their association with ovarian cancer risk. A search of MEDLINE bibliographic database for the period up to April 2012 identified five studies. With regards to Leu432Val polymorphism, all of the five studies were eligible (1199 cases and 2596 controls) for analysis, while for Arg48Gly (799 cases and 1169 controls), Ala119Ser (799 cases and 1172 controls) and Asn453Ser (361cases and 1577 controls) only two studies were eligible for analysis. Fixed-effect models were used to estimate pooled odds ratios (OR) with 95% confidence intervals (95% CI) and chi-square based Q-test was used to test for heterogeneity. The pooled OR (95% CI) for CYP1B1_Leu432Val polymorphism were 1.1 (0.84-1.31) for heterozygous subjects and 0.82 (0.57-1.17) for homozygous Val subjects. In a recessive model, homozygous carriers of Leu432Val showed a weak trend towards reduced risk as compared to 'wild type' and heterozygous carriers (OR 0.8, 95% CI; 0.66-0.99); however, this association was of limited significance. Regarding Arg48Gly, the pooled OR (95% CI) were 1.06 (0.89-1.27) for heterozygous and 0.98 (1.72-1.33) for homozygous Gly subjects. With respect to Ala119Ser and Asn453Ser, the pooled OR were 1.06 (0.87-1.29) and 1.24 (0.94-1.63) for heterozygous and 1.1 (0.8-1.52) and 1.09 (0.5-2.34) for homozygous respectively. In conclusion, this meta-analysis suggests that CYP1B1 polymorphisms are not associated with ovarian cancer risk. Studies evaluating CYP1B1_Leu432Val polymorphism are required to further elucidate the risk of ovarian cancer with this polymorphism. Additionally, studies amongst Asian and African subjects are required to estimate race-specific effects.

Item Type: Article
Journal or Publication Title: Toxicology
Additional Information: Copyright © 2012. Published by Elsevier Ireland Ltd.
Uncontrolled Keywords: Ala119Ser ; Arg48Gly ; Asn453Ser ; CYP1B1 polymorphism ; Leu432Val ; Ovarian cancer
Subjects: Q Science > QA Mathematics
Departments: Faculty of Science and Technology > Mathematics and Statistics
Faculty of Science and Technology > Lancaster Environment Centre
Faculty of Health and Medicine > Medicine
ID Code: 59615
Deposited By: ep_importer_pure
Deposited On: 29 Oct 2012 09:38
Refereed?: Yes
Published?: Published
Last Modified: 01 Oct 2013 15:30
Identification Number:
URI: http://eprints.lancs.ac.uk/id/eprint/59615

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