Thorlacius S, Olafsdottir G, Tryggvadottir L, Neuhausen S, Jonasson J G, Tavtigian S V, Tulinius H, Ogmundsdottir H M, Eyfjörd J E
Molecular and Cell Biology Research Laboratory, Icelandic Cancer Society, Reykjavik, Iceland.
Nat Genet. 1996 May;13(1):117-9. doi: 10.1038/ng0596-117.
The BRCA2 gene on chromosome 13 has been shown to be associated with familial male and female breast cancer. Here we describe a study on BRCA2 in 21 Icelandic families, including 9 with male breast cancer. We have previously reported linkage to the BRCA2 region in an Icelandic male breast cancer family and subsequently found a strong indication of linkage to BRCA2 and the same BRCA2 haplotype in breast cancer cases from 15 additional families, indicating a common origin. We describe a five base-pair deletion in exon 9 of BRCA2 in an affected male from the male breast cancer family. The same mutation occurs in all the families with the shared BRCA2 haplotype indicating a founder effect. Among mutation carriers there are 12 males with breast cancer, which accounts for 40% of all males diagnosed with breast cancer in Iceland over the past 40 years. Three of them have no family history of breast cancer indicating that this mutation may have variable penetrance. The same BRCA2 mutation appears to be associated with different cancer phenotypes in this population including male and female breast cancer, prostate cancer, pancreas cancer and ovarian cancer.
13号染色体上的BRCA2基因已被证明与家族性男性和女性乳腺癌有关。在此，我们描述了一项对21个冰岛家族中BRCA2基因的研究，其中包括9个有男性乳腺癌患者的家族。我们之前报道过在一个冰岛男性乳腺癌家族中与BRCA2区域存在连锁关系，随后在另外15个家族的乳腺癌病例中也发现了与BRCA2以及相同BRCA2单倍型存在强烈连锁的迹象，这表明它们有共同的起源。我们描述了一名来自男性乳腺癌家族的患病男性中BRCA2基因第9外显子存在一个5个碱基对的缺失。在所有具有共享BRCA2单倍型的家族中都出现了相同的突变，这表明存在奠基者效应。在突变携带者中有12名男性患有乳腺癌，这占过去40年冰岛所有被诊断出患有乳腺癌男性的40%。其中3人没有乳腺癌家族史，这表明该突变可能具有可变的外显率。在这个人群中，相同的BRCA2突变似乎与不同的癌症表型有关，包括男性和女性乳腺癌、前列腺癌、胰腺癌和卵巢癌。
