Germ-line BRCA1 mutations in Jewish and non-Jewish women with early-onset breast cancer
Germ-line BRCA1 mutations in Jewish and non-Jewish women with early-onset breast cancer
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DOI：
10.1056/nejm199601183340302
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发表时间：
1996-01-18
影响因子：
158.5
通讯作者：
Haber, DA
中科院分区：
文献类型：
--
作者：
FitzGerald, MG;MacDonald, DJ;Haber, DA
背景。 BRCA1 基因的生殖系等位基因突变会导致家族性乳腺癌综合征。然而，这些突变在不具有这种家族综合征特征的乳腺癌女性中的患病率尚不清楚。我们在年轻时被诊断出乳腺癌的女性中寻找 BRCA1 突变，因为早发是癌症遗传易感性的特征。方法。研究人员从波士顿都会区 418 名在 40 岁或之前被诊断出乳腺癌的女性中获得了临床信息和外周血单核细胞。对其中 30 名在 30 岁之前患有乳腺癌的女性进行了全面的 BRCA1 突变分析，包括自动核苷酸测序和蛋白质截短测定。此外，还寻找了德系犹太人中普遍存在的 BRCA1 突变 185delAG对 418 名 40 岁或之前患有乳腺癌的女性中的 39 名犹太女性进行了等位基因特异性聚合酶链反应测定。结果。在 30 名 30 岁之前患有乳腺癌的女性中，4 人（13%）有明确的链终止突变，1 人有错义突变。该队列中的四名犹太女性中有两名患有 185delAG 突变。在 40 岁或之前患乳腺癌的 39 名犹太女性中，8 名 (21%) 携带 185delAG 突变（95% 置信区间，9% 至 36%）。结论。生殖系 BRCA1 突变可能存在于不属于有多位受影响成员的家庭的患有乳腺癌的年轻女性中。被称为 185delAG 的特定 BRCA1 突变与 40 岁之前犹太女性乳腺癌的发病密切相关。
Background. Mutations in a germ-line allele of the BRCA1 gene contribute to the familial breast cancer syndrome. However, the prevalence of these mutations is unknown in women with breast cancer who do not have the features of this familial syndrome. We sought BRCA1 mutations in women who were given a diagnosis of breast cancer at an early age, because early onset is characteristic of a genetic predisposition to cancer.Methods. Clinical information and peripheral-blood mononuclear cells were obtained from 418 women from the Boston metropolitan area in whom breast cancer was diagnosed at or before the age of 40. A comprehensive BRCA1 mutational analysis, involving automated nucleotide sequencing and a protein-truncation assay, was undertaken in 30 of these women, who had breast cancer before the age of 30. In addition, the BRCA1 mutation 185delAG, which is prevalent in the Ashkenazi Jewish population, was sought with an allele-specific polymerase-chain-reaction assay in 39 Jewish women among the 418 women who had breast cancer at or before the age of 40.Results. Among 30 women with breast cancer before the age of 30, 4 (13 percent) had definite, chain-terminating mutations and 1 had a missense mutation. Two of the four Jewish women in this cohort had the 185delAG mutation, Among the 39 Jewish women with breast cancer at or before the age of 40, 8 (21 percent) carried the 185delAG mutation (95 percent confidence interval, 9 to 36 percent).Conclusions. Germ-line BRCA1 mutations can be present in young women with breast cancer who do not belong to families with multiple affected members. The specific BRCA1 mutation known as 185delAG is strongly associated with the onset of breast cancer in Jewish women before the age of 40.