Seal Sheila, Thompson Deborah, Renwick Anthony, Elliott Anna, Kelly Patrick, Barfoot Rita, Chagtai Tasnim, Jayatilake Hiran, Ahmed Munaza, Spanova Katarina, North Bernard, McGuffog Lesley, Evans D Gareth, Eccles Diana, Easton Douglas F, Stratton Michael R, Rahman Nazneen
Section of Cancer Genetics, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK.
Nat Genet. 2006 Nov;38(11):1239-41. doi: 10.1038/ng1902. Epub 2006 Oct 8.
We identified constitutional truncating mutations of the BRCA1-interacting helicase BRIP1 in 9/1,212 individuals with breast cancer from BRCA1/BRCA2 mutation-negative families but in only 2/2,081 controls (P = 0.0030), and we estimate that BRIP1 mutations confer a relative risk of breast cancer of 2.0 (95% confidence interval = 1.2-3.2, P = 0.012). Biallelic BRIP1 mutations were recently shown to cause Fanconi anemia complementation group J. Thus, inactivating truncating mutations of BRIP1, similar to those in BRCA2, cause Fanconi anemia in biallelic carriers and confer susceptibility to breast cancer in monoallelic carriers.
我们在1212名来自BRCA1/BRCA2突变阴性家族的乳腺癌患者中，发现了9例与BRCA1相互作用的解旋酶BRIP1的胚系截短突变，但在2081名对照者中仅发现2例（P = 0.0030）。我们估计，BRIP1突变导致患乳腺癌的相对风险为2.0（95%置信区间 = 1.2 - 3.2，P = 0.012）。最近研究表明，双等位基因BRIP1突变可导致范可尼贫血J互补组疾病。因此，与BRCA2中的突变类似，BRIP1的失活截短突变在双等位基因携带者中会导致范可尼贫血，而在单等位基因携带者中会增加患乳腺癌的易感性。
