FitzGerald M G, MacDonald D J, Krainer M, Hoover I, O'Neil E, Unsal H, Silva-Arrieto S, Finkelstein D M, Beer-Romero P, Englert C, Sgroi D C, Smith B L, Younger J W, Garber J E, Duda R B, Mayzel K A, Isselbacher K J, Friend S H, Haber D A
Center for Cancer Risk Analysis, Charlestown, Mass, USA.
N Engl J Med. 1996 Jan 18;334(3):143-9. doi: 10.1056/NEJM199601183340302.
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.
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.
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).
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.
BRCA1基因种系等位基因突变与家族性乳腺癌综合征有关。然而，在不具有这种家族综合征特征的乳腺癌女性中，这些突变的发生率尚不清楚。我们在早年被诊断为乳腺癌的女性中寻找BRCA1突变，因为发病早是癌症遗传易感性的特征。
从波士顿市区的418名在40岁及以前被诊断为乳腺癌的女性中获取临床信息和外周血单个核细胞。对其中30名在30岁以前患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试验。此外，在418名40岁及以前患乳腺癌的女性中的39名犹太女性中，采用等位基因特异性聚合酶链反应试验寻找在阿什肯纳兹犹太人群中普遍存在的BRCA1突变185delAG。
在年龄小于30岁的30名乳腺癌女性中，4名（13%）有明确的链终止突变，1名有一个错义突变。该队列中的4名犹太女性中有2名有185delAG突变。在39名40岁及以前患乳腺癌的犹太女性中，8名（21%）携带185delAG突变（95%可信区间为9%至36%）。
种系BRCA1突变可存在于不属于有多个患病成员家族的年轻乳腺癌女性中。名为185delAG的特定BRCA1突变与40岁以前犹太女性乳腺癌的发病密切相关。
