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Carcinogenesis Advance Access originally published online on May 25, 2005
Carcinogenesis 2005 26(10):1651-1656; doi:10.1093/carcin/bgi136
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Carcinogenesis vol.26 no.10 © Oxford University Press 2005; all rights reserved.

COMMENTARY

BRCA1 and BRCA2 as ovarian cancer susceptibility genes

Heidi M. Sowter and Alan Ashworth *

The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, Fulham Road, London SW3 6JB, UK

* To whom correspondence should be addressed. Tel: 0207 970 6058; Fax: 0207 878 3858; Email: alan.ashworth{at}icr.ac.uk

Individuals carrying germline mutations in one allele of the BRCA1 or BRCA2 genes are at significantly increased risk of developing cancer. Although the increased risk of breast cancer is often highlighted, cancer at several other sites is also considerably more common in these individuals. Here, we discuss existing knowledge of the role of BRCA1 and BRCA2 mutation in pre-disposition to ovarian cancer. The risk of an individual with a mutation developing cancer of the ovary appears to be influenced by the position of the mutation within the BRCA gene, the presence of allelic variants of modifying genes and the hormonal exposure of the carrier. Once cancer has developed, the pathology and clinical behaviour of BRCA-associated tumours is distinct from sporadic cases. Comparison of the pathogenesis of breast and ovarian cancers caused by BRCA mutation provides insight into the function of BRCA proteins as tumour suppressors in different cellular environments.


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