BRCA1 variants in a family study of African-American and Latina women
BRCA1 variants in a family study of African-American and Latina women
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DOI：
10.1007/s00439-004-1240-5
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发表时间：
2005-05-01
期刊：
影响因子：
5.3
通讯作者：
Henderson, BE
中科院分区：
文献类型：
--
作者：
McKean-Cowdin, R;Feigelson, HS;Henderson, BE
我们对BRCA 1的整个编码区进行测序，以提高我们对从加州洛杉矶多种族队列中确定的非洲裔美国人和拉丁裔妇女BRCA 1变异的频率和性质的理解。这项研究包括109名非洲裔美国人和140名拉丁裔同胞，他们来自一级亲属中有两例或更多乳腺癌或卵巢癌病例的家庭。对278例乳腺癌或卵巢癌病例和229例未受影响的姐妹篇进行了BRCA 1测序。已知致病突变的病例比例较低（0.72，95%置信区间：0-1.7%）。总共鉴定了33种序列变体，包括2种蛋白质截短突变、1种缺失、6种沉默变体和24种错义变体。两个新的罕见变异被确定为良性多态性。根据现有文献，四种罕见的变异可能是非洲裔妇女所独有的，三种变异仅在拉丁裔妇女中描述。病例和对照组的常见变异频率相似，但非裔美国妇女的常见变异频率与先前描述的白人妇女的常见变异频率显著不同。我们相信这是迄今为止对高危非洲裔美国人和拉丁裔妇女进行BRCA 1基因变异测序的最大规模的研究。
We sequenced the entire coding region of BRCA1 to improve our understanding of the frequency and nature of BRCA1 variants in African-American and Latina women identified from a multiethnic cohort in Los Angeles, California. The study included 109 African-American and 140 Latina sibships from families with two or more cases of breast or ovarian cancer among first-degree relatives. BRCA1 was sequenced in 278 breast or ovarian cancer cases and 229 unaffected sisters. The proportion of cases with known disease-causing mutations was low (0.72, 95% confidence interval: 0-1.7%). In total, 33 sequence variants were identified, including two protein truncation mutations, one deletion, and six silent and 24 missense variants. Two novel rare variants were identified that appeared to act as benign polymorphisms. Four rare variants may be unique to women of African descent based on existing literature, and three have been described exclusively in Latina women. The frequency of common variants was similar for cases and controls, but the frequency of common variants for African-American women significantly differed from those previously described for Caucasian women. We believe this to be the largest study of high-risk African-American and Latina women sequenced for variants in the BRCA1 gene to date.