High sensitivity for BRCA1/2 mutations in breast/ovarian kindreds: are there still other breast/ovary genes to be discovered?
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To the editor,
Recently, two genes RAD51C  and RAD51D  have been identified as high-risk ovarian cancer genes. However, their contribution to breast cancer risk is less clear . Indeed a recent analysis of both genes in the familial breast cancer study (FBCS) cohort has not suggested any increased risk of breast cancer, but a 6–8 fold increase in ovarian cancer risk for both genes . We show here that the contribution of RAD51C and RAD51D gene mutations to an inherited high risk of ovarian cancer is very small.
Until the discovery of pathogenic mutations in RAD51C and RAD51D, it was assumed that the majority, if not all, of the inherited breast and ovarian cancer was due to mutations in BRCA1 or BRCA2 . Ninety-five percent of families with the breast cancer linkage consortium (BCLC) criteria of at least four breast or ovarian cancers with the breast cancers diagnosed <60 years of age and at least one ovarian cancer in the family were predicted to have a mutation in either...
KeywordsBreast Cancer Ovarian Cancer Ovarian Cancer Risk High Risk Family Ovarian Cancer Family
D. G. E., W. G. N. and F. L. are supported by the NIHR Biomedical Research Centre, Manchester. Additional grant support was from The Genesis Breast Cancer Prevention Appeal. We would also like to thank Prof Nazneen Rahman and her team at ICR for supplying us with the RAD51D results and contributing towards RAD51C testing.
- 1.Meindl A, Hellebrand H, Wiek C, Erven V, Wappenschmidt B, Niederacher D, Freund M, Lichtner P, Hartmann L, Schaal H, Ramser J, Honisch E, Kubisch C, Wichmann HE, Kast K, Deissler H, Engel C, Müller-Myhsok B, Neveling K, Kiechle M, Mathew CG, Schindler D, Schmutzler RK, Hanenberg H (2010) Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene. Nat Genet 42(5):410–414PubMedCrossRefGoogle Scholar
- 2.Loveday C, Turnbull C, Ramsay E, Hughes D, Ruark E, Frankum JR, Bowden G, Kalmyrzaev B, Warren-Perry M, Snape K, Adlard JW, Barwell J, Berg J, Brady AF, Brewer C, Brice G, Chapman C, Cook J, Davidson R, Donaldson A, Douglas F, Greenhalgh L, Henderson A, Izatt L, Kumar A, Lalloo F, Miedzybrodzka Z, Morrison PJ, Paterson J, Porteous M, Rogers MT, Shanley S, Walker L, Breast Cancer Susceptibility Collaboration (UK), Eccles D, Evans DG, Renwick A, Seal S, Lord CJ, Ashworth A, Reis-Filho JS, Antoniou AC, Rahman N (2011) Germline mutations in RAD51D confer susceptibility to ovarian cancer. Nat Genet 43(9):879–882. doi: 10.1038/ng.893 PubMedCrossRefGoogle Scholar
- 3.Loveday C, Turnbull C, Ruark E, Xicola R, Ramsay E, Hughes D, Warren- Perry M, Snape K, Breast Cancer Susceptibility Collaboration (UK), Eccles D, Evans DG, Renwick A, Renwick A, Seal S, Reis-Filho JS, Antoniou AC, Rahman N (2012) Germline RAD51C mutations confer susceptibility to ovarian cancer. Nat Genet 44(5):475–476Google Scholar
- 4.Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, Bishop DT, Weber B, Lenoir G, Chang-Claude J, Sobol H, Teare MD, Struewing J, Arason A, Scherneck S, Peto J, Rebbeck TR, Tonin P, Neuhausen S, Barkardottir R, Eyfjord J, Lynch H, Ponder BAJ, Gayther SA, Birch JM, Lindblom A, Stoppa-Lyonnet D, Bignon Y, Borg A, Hamann U, Haites N, Scott RJ, Maugard CM, Vasen H, Seitz S, Cannon-Albright LA, Schofield A, Zelada-Hedman M and The Breast Cancer Linkage Consortium (1998) Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. Am J Hum Genet 62(3):676–689Google Scholar