PMID- 21822267
OWN - NLM
STAT- Publisher
DA  - 20110808
IS  - 1546-1718 (Electronic)
IS  - 1061-4036 (Linking)
DP  - 2011 Aug 7
TI  - Germline mutations in RAD51D confer susceptibility to ovarian cancer.
LID - 10.1038/ng.893 [doi]
AB  - 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 x 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.
AD  - 1] Section of Cancer Genetics, The Institute of Cancer Research, Sutton, UK. [2].
AU  - Loveday C
AU  - Turnbull C
AU  - Ramsay E
AU  - Hughes D
AU  - Ruark E
AU  - Frankum JR
AU  - Bowden G
AU  - Kalmyrzaev B
AU  - Warren-Perry M
AU  - Snape K
AU  - Adlard JW
AU  - Barwell J
AU  - Berg J
AU  - Brady AF
AU  - Brewer C
AU  - Brice G
AU  - Chapman C
AU  - Cook J
AU  - Davidson R
AU  - Donaldson A
AU  - Douglas F
AU  - Greenhalgh L
AU  - Henderson A
AU  - Izatt L
AU  - Kumar A
AU  - Lalloo F
AU  - Miedzybrodzka Z
AU  - Morrison PJ
AU  - Paterson J
AU  - Porteous M
AU  - Rogers MT
AU  - Shanley S
AU  - Walker L
CN  - Breast Cancer Susceptibility Collaboration (UK)
AU  - Eccles D
AU  - Evans DG
AU  - Renwick A
AU  - Seal S
AU  - Lord CJ
AU  - Ashworth A
AU  - Reis-Filho JS
AU  - Antoniou AC
AU  - Rahman N
LA  - ENG
PT  - JOURNAL ARTICLE
DEP - 20110807
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
EDAT- 2011/08/09 06:00
MHDA- 2011/08/09 06:00
CRDT- 2011/08/09 06:00
PHST- 2011/03/03 [received]
PHST- 2011/07/01 [accepted]
PHST- 2011/08/07 [aheadofprint]
AID - ng.893 [pii]
AID - 10.1038/ng.893 [doi]
PST - aheadofprint
SO  - Nat Genet. 2011 Aug 7. doi: 10.1038/ng.893.