Prevalence of BRCA1 and BRCA2 mutations in Pakistani breast and ovarian cancer patients
Prevalence of BRCA1 and BRCA2 mutations in Pakistani breast and ovarian cancer patients
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DOI：
10.1002/ijc.22269
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发表时间：
2006-12-15
影响因子：
6.4
通讯作者：
Hamann, Ute
中科院分区：
文献类型：
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作者：
Rashid, Muhammad U.;Zaidi, Anbreen;Hamann, Ute
在亚洲国家中，巴基斯坦的乳腺癌和卵巢癌发病率最高。为了评估BRCA1和BRCA2胚系突变对这些高发病率的贡献，我们对176名巴基斯坦乳腺癌和卵巢癌患者进行了第一次研究，这些患者是根据家族史和诊断年龄选择的。采用变性高压液相色谱、单链构象多态分析和蛋白质截断试验等多种技术进行BRCA基因突变筛查，并进行DNA测序。在176个家系中发现了30个有害的生殖系突变(17.0%)，其中BRCA1基因突变23个，BRCA2基因突变7个。185delAG、185insA、S1503X和R1835X这4个突变是复发的，占所有已鉴定的BRCA1突变的52%。单倍型分析表明，其中3个基因存在创始人效应。BRCA1或BRCA2突变在多发乳腺癌家系中的发生率为42.8%，在乳腺癌/卵巢癌家系中为50.0%。单例早发性乳腺癌的突变发生率为11.9%(
Among Asian countries, Pakistan has the highest rates of breast and ovarian cancer. To assess the contribution of the BRCA1 and BRCA2 germ line mutations to these high rates, we conducted the first study of 176 Pakistani breast and ovarian cancer patients, selected on family history and on age of diagnosis. Comprehensive BRCA mutation screening was performed using a range of techniques, including denaturing high-pressure liquid chromatography, single strand conformational polymorphism analysis and protein truncation test, followed by DNA sequencing. Thirty deleterious germ-line mutations were identified in the 176 families (17.0%), including 23 in BRCA1 and 7 in BRCA2. Four mutations, 185delAG, 185insA, S1503X and R1835X, were recurrent; these accounted for 52% of all identified BRCA1 mutations. Haplotype analyses suggested founder effects for 3 of these. The prevalence of BRCA1 or BRCA2 mutations was 42.8% for families with multiple cases of breast cancer, and was 50.0% for the breast/ovarian cancer families. The prevalence of mutations was 11.9% for single cases of early-onset breast cancer (