Sopik V, Akbari M R, Narod S A
Women's College Research Institute, Women's College Hospital, University of Toronto, Toronto, Ontario, M5G 1N8, Canada.
Clin Genet. 2015 Oct;88(4):303-12. doi: 10.1111/cge.12548. Epub 2015 Jan 7.
Much of the observed familial clustering of breast and ovarian cancer cannot be explained by mutations in BRCA1 and BRCA2. Several other cancer susceptibility genes have been identified, but their value in routine clinical genetic testing is still unclear. Germline mutations in RAD51C have been identified in about 1% of hereditary breast and ovarian cancer families. RAD51C mutations are predominantly found in families with a history of ovarian cancer and are rare in families with a history of breast cancer alone. RAD51C is primarily an ovarian cancer susceptibility gene. A mutation is present in approximately 1% of unselected ovarian cancers. Among mutation carriers, the lifetime risk of ovarian cancer is approximately 9%. The average age at onset is approximately 60 years; this suggests that preventive oophorectomy can be delayed until after natural menopause. Under current guidelines, genetic testing for RAD51C is expected to have a limited impact on ovarian cancer incidence at a population level. This is because the penetrance is 9% to age 80; the great majority of families with mutations would be represented by a single case of ovarian cancer, these are potentially preventable through population screening but not through screening of established ovarian cancer families.
乳腺癌和卵巢癌所观察到的家族聚集现象，很多无法用BRCA1和BRCA2的突变来解释。已经鉴定出了其他几个癌症易感基因，但其在常规临床基因检测中的价值仍不明确。在约1%的遗传性乳腺癌和卵巢癌家族中发现了RAD51C的种系突变。RAD51C突变主要见于有卵巢癌病史的家族，而在仅有乳腺癌病史的家族中罕见。RAD51C主要是一种卵巢癌易感基因。在约1%的未经选择的卵巢癌中存在突变。在突变携带者中，卵巢癌的终生风险约为9%。平均发病年龄约为60岁；这表明预防性卵巢切除术可推迟至自然绝经后。根据现行指南，RAD51C的基因检测预计在人群水平上对卵巢癌发病率的影响有限。这是因为至80岁时的外显率为9%；绝大多数有突变的家族将仅出现一例卵巢癌病例，这些病例可通过人群筛查而非通过对已确诊的卵巢癌家族进行筛查来预防。
