Neuhausen S, Gilewski T, Norton L, Tran T, McGuire P, Swensen J, Hampel H, Borgen P, Brown K, Skolnick M, Shattuck-Eidens D, Jhanwar S, Goldgar D, Offit K
Department of Human Genetics, Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Nat Genet. 1996 May;13(1):126-8. doi: 10.1038/ng0596-126.
The lifetime risk of breast cancer may approach 80-90% in women who have germline mutations of either of two genes, BRCA1 or BRCA2. A single BRCA1 mutation, 185delAG, has been noted in approximately 20% of Ashkenazi Jewish women with early onset breast cancer and in 0.9% of the Ashkenazi population. We recently detected a 6174delT frameshift mutation in BRCA2 in an hereditary breast cancer kindred of Ashkenazi Jewish ancestry. Here, we investigated the frequency of this mutation in 200 women with early-onset breast cancer. Six of 80 Ashkenazi Jewish women (8%) diagnosed with breast cancer before the age of 42, wer heterozygous for the 6174delT mutation, compared to none of 93 non-Jewish women diagnosed with breast cancer at the same age (P = .005). These cases were ascertained without regard to family history. Two of 27 (7%) additional Jewish families in which the proband was diagnosed with breast cancer at age 42 to 50 and had a family history of breast or ovarian cancer had germline 6174delT mutations. The results of this report suggest that a recurrent mutation of BRCA1 and a recurrent mutation BRCA2 together may account for over a quarter of all early-onset breast cancer in the setting of a personal or family history of ovarian cancer in Ashkenazi Jewish women.
对于携带BRCA1或BRCA2这两种基因中任何一种种系突变的女性，患乳腺癌的终生风险可能接近80 - 90%。在大约20%的阿什肯纳兹犹太族早发性乳腺癌女性以及0.9%的阿什肯纳兹人群中，已发现一种BRCA1突变，即185delAG。我们最近在一个阿什肯纳兹犹太族遗传乳腺癌家族中检测到BRCA2基因的6174delT移码突变。在此，我们调查了该突变在200名早发性乳腺癌女性中的频率。80名在42岁之前被诊断为乳腺癌的阿什肯纳兹犹太族女性中有6名（8%）为6174delT突变杂合子，而93名同年龄段被诊断为乳腺癌的非犹太族女性中无一例出现该突变（P = .005）。这些病例是在不考虑家族史的情况下确定的。在另外27个犹太族家庭中，先证者在42至50岁被诊断为乳腺癌且有乳腺癌或卵巢癌家族史，其中有2个家庭（7%）存在种系6174delT突变。本报告结果表明，在阿什肯纳兹犹太族女性有个人或家族卵巢癌病史的情况下，BRCA1的一种复发性突变和BRCA2的一种复发性突变共同可能占所有早发性乳腺癌的四分之一以上。
