Laboratory of Cancer Genetics, Department of Clinical Genetics and Biocenter Oulu, University of Oulu, Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland.
Breast Cancer Res Treat. 2011 Dec;130(3):1003-10. doi: 10.1007/s10549-011-1677-x. Epub 2011 Jul 13.
RAD51C, a RAD51 paralogue involved in homologous recombination, is a recently established Fanconi anemia and breast cancer predisposing factor. In the initial report, RAD51C mutations were shown to confer a high risk for both breast and ovarian tumors, but most of the replication studies published so far have failed to identify any additional susceptibility alleles. Here, we report a full mutation screening of the RAD51C gene in 147 Finnish familial breast cancer cases and in 232 unselected ovarian cancer cases originating from Finland and Sweden. In addition, in order to resolve whether common RAD51C SNPs are risk factors for breast cancer, we genotyped five tagging single nucleotide polymorphisms, rs12946522, rs304270, rs304283, rs17222691, and rs28363312, all located within the gene, from 993 Finnish breast cancer cases and 871 controls for cancer associated variants. Whereas, none of the studied common SNPs associated with breast cancer susceptibility, mutation analysis revealed two clearly pathogenic alterations. RAD51C c.-13_14del27 was observed in one familial breast cancer case and c.774delT in one unselected ovarian cancer case, thus confirming that RAD51C mutations are implicated in breast and ovarian cancer predisposition, although their overall frequency seems to be low. Independent identification of the very recently reported RAD51C c.774delT mutation in yet another patient originating from Sweden suggests that it might be a recurrent mutation in that population and should be studied further. The reliable estimation of the clinical implications of carrying a defective RAD51C allele still requires the identification of additional mutation positive families.
RAD51C 是一种 RAD51 同源重组相关的蛋白，最近被认为是范可尼贫血症和乳腺癌的易感基因。在最初的报道中，RAD51C 突变被证实与乳腺癌和卵巢癌的高风险相关，但迄今为止发表的大多数复制研究都未能发现其他易感等位基因。在这里，我们对来自芬兰和瑞典的 147 例家族性乳腺癌病例和 232 例未选择的卵巢癌病例进行了 RAD51C 基因的全面突变筛查。此外，为了确定常见的 RAD51C SNPs 是否是乳腺癌的风险因素，我们对来自芬兰的 993 例乳腺癌病例和 871 例对照进行了位于该基因内的五个标记单核苷酸多态性 rs12946522、rs304270、rs304283、rs17222691 和 rs28363312 的基因分型，以研究与癌症相关的变异。然而，没有一个研究的常见 SNP 与乳腺癌易感性相关，突变分析显示了两个明显的致病性改变。RAD51C c.-13_14del27 存在于一个家族性乳腺癌病例中，c.774delT 存在于一个未选择的卵巢癌病例中，因此证实 RAD51C 突变与乳腺癌和卵巢癌易感性有关，尽管它们的总体频率似乎较低。在另一个来自瑞典的患者中独立鉴定出最近报道的 RAD51C c.774delT 突变，表明它可能是该人群中的一种复发性突变，应该进一步研究。可靠地评估携带缺陷 RAD51C 等位基因的临床意义仍然需要确定其他突变阳性家族。
