| Literature DB >> 21822267 |
Chey Loveday1, Clare Turnbull1, Emma Ramsay1, Deborah Hughes1, Elise Ruark1, Jessica R Frankum2, Georgina Bowden1, Bolot Kalmyrzaev1, Margaret Warren-Perry1, Katie Snape1, Julian W Adlard3, Julian Barwell4, Jonathan Berg5, Angela F Brady6, Carole Brewer7, Glen Brice8, Cyril Chapman9, Jackie Cook10, Rosemarie Davidson11, Alan Donaldson12, Fiona Douglas13, Lynn Greenhalgh14, Alex Henderson15, Louise Izatt16, Ajith Kumar17, Fiona Lalloo18, Zosia Miedzybrodzka19, Patrick J Morrison20, Joan Paterson21, Mary Porteous22, Mark T Rogers23, Susan Shanley24, Lisa Walker25, Diana Eccles26, D Gareth Evans18, Anthony Renwick1, Sheila Seal1, Christopher J Lord2, Alan Ashworth2, Jorge S Reis-Filho2, Antonis C Antoniou27, Nazneen Rahman1.
Abstract
Recently, RAD51C mutations were identified in families with breast and ovarian cancer. This observation prompted us to investigate the role of RAD51D in cancer susceptibility. We identified eight inactivating RAD51D mutations in unrelated individuals from 911 breast-ovarian cancer families compared with one inactivating mutation identified in 1,060 controls (P = 0.01). The association found here was principally with ovarian cancer, with three mutations identified in the 59 pedigrees with three or more individuals with ovarian cancer (P = 0.0005). The relative risk of ovarian cancer for RAD51D mutation carriers was estimated to be 6.30 (95% CI 2.86-13.85, P = 4.8 × 10(-6)). By contrast, we estimated the relative risk of breast cancer to be 1.32 (95% CI 0.59-2.96, P = 0.50). These data indicate that RAD51D mutation testing may have clinical utility in individuals with ovarian cancer and their families. Moreover, we show that cells deficient in RAD51D are sensitive to treatment with a PARP inhibitor, suggesting a possible therapeutic approach for cancers arising in RAD51D mutation carriers.Entities:
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Year: 2011 PMID： 21822267 PMCID： PMC4845885 DOI： 10.1038/ng.893
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330