Cross-sectional analysis of germline BRCA1 and BRCA2 mutations in Japanese patients suspected to have hereditary breast/ovarian cancer
Cross-sectional analysis of germline BRCA1 and BRCA2 mutations in Japanese patients suspected to have hereditary breast/ovarian cancer
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DOI：
10.1111/j.1349-7006.2008.00944.x
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发表时间：
2008-10-01
期刊：
影响因子：
5.7
通讯作者：
Miki, Yoshio
中科院分区：
文献类型：
--
作者：
Sugano, Kokichi;Nakamura, Seigo;Miki, Yoshio
一项多机构研究调查了怀疑患有遗传性乳腺癌/卵巢癌的日本患者中BRCA1/2胚系突变的发生率，旨在研究全序列分析在日本人中的临床应用，并使用基于个人和家族病史估计的遗传因素的横断面方法验证检测敏感性。135名受试者被转介到遗传咨询诊所，并参加了这项研究。对BRCA1/2基因进行全序列分析，发现36例(26.7%)患者存在28种有害突变，其中BRCA1基因突变17例(12.6%)，BRCA2基因突变19例(14.1%)。受试者根据其乳腺癌和/或卵巢癌的个人和家族病史被分为五组和22个亚组，并将有害突变的患病率与之前报道的非德系克肯纳齐族人的数据进行了比较。用Mantel-Haenszel检验对I~IV组进行统计分析发现，日本人的患病率显著高于非德系犹太人(P=0.005，优势比1.87，95%可信区间1.22~2.88)。乳腺癌先证者家族史显示BRCA1/2恶性突变的危险因素如下：(1)40岁以前的二级亲属中有乳腺癌(P=0.0265，优势比2.833，95%可信区间1.165~7.136)；(2)二级亲属中有双侧乳腺癌和/或卵巢癌(P=0.0151，优势比2.88，95%可信区间1.25~6.64)。(《癌症科学》2008；99：1967-1976)。
The prevalence of BRCA1/2 germline mutations in Japanese patients suspected to have hereditary breast/ovarian cancer was examined by a multi-institutional study, aiming at the clinical application of total sequencing analysis and validation of assay sensitivity in Japanese people using a cross-sectional approach based on genetic factors estimated from personal and family histories. One hundred and thirty-five subjects were referred to the genetic counseling clinics and enrolled in the study. Full sequencing analysis of the BRCA1/2 gene showed 28 types of deleterious mutations in 36 subjects (26.7%), including 13 types of BRCA1 mutations in 17 subjects (12.6%) and 15 types of BRCA2 mutations in 19 subjects (14.1%). Subjects were classified into five groups and 22 subgroups according to their personal and family history of breast and/or ovarian cancer, and the prevalence of deleterious mutations was compared with previously reported data in non-Ashkenazi individuals. Statistical analysis using the Mantel-Haenszel test for groups I through IV revealed that the prevalence of Japanese subjects was significantly higher than that of non-Ashkenazi individuals (P = 0.005, odds ratio 1.87, 95% confidence interval 1.22-2.88). Family history of the probands suffering from breast cancer indicated risk factors for the presence of deleterious mutations of BRCA1/2 as follows: (1) families with breast cancer before age 40 within second degree relatives (P = 0.0265, odds ratio 2.833, 95% confidence interval 1.165-7.136) and (2) families with bilateral breast cancer and/or ovarian cancer within second degree relatives (P = 0.0151, odds ratio 2.88, 95% confidence interval 1.25-6.64). (Cancer Sci 2008; 99: 1967-1976).