Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer
Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer
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DOI：
10.1093/jnci/91.11.943
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发表时间：
1999-06-02
期刊：
影响因子：
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通讯作者：
Stratton, MR
中科院分区：
文献类型：
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作者：
Peto, J;Collins, N;Stratton, MR
背景资料：BRCA 1和BRCA 2基因突变在大多数乳腺癌和卵巢癌或早发性乳腺癌的家族中发现，然而，在远交人群中，BRCA 1和BRCA 2突变在乳腺癌患者中的患病率尚未确定。研究方法：BRCA 1和BRCA 2基因的突变是在来自英国的两个基于人群的年轻乳腺癌患者的血液样本中检测到的。结果如下：在254名36岁之前被诊断患有乳腺癌的女性中，有15名（5.9%）检测到突变（BRCA 1中有9名[3.5%]，BRCA 2中有6名[2.4%]），在36岁至45岁期间诊断的363名女性中，有15名（4.1%）检测到突变（BRCA 1中有7名[1.9%]，BRCA 2中有8名[2.2%]）。百分之十一60岁时有一级亲属患卵巢癌或乳腺癌的患者中有65例是突变携带者，而60岁时有45%是突变携带者。（5/11）有两个或更多受影响的一级或二级亲属的患者，母亲和姐妹篇乳腺癌的标化发病比为365（观察到5例，预期1.37例），587例非携带者为199例（观察到64例，预期32.13例）。如果我们假设最近的突变率估计，BRCA 1和BRCA 2突变携带者的比例分别为3.1%和3.0%，在50岁以下的乳腺癌患者中，分别为0.49%和0.84%，在50岁或以上的乳腺癌患者中，分别为0.11%和0.12%。结论：BRCA 1和BRCA 2基因突变对英国早发性乳腺癌的贡献大致相同，并且占乳腺癌家族风险的一小部分。
Background: Mutations in the BRCA1 and BRCA2 genes are found in most families with cases of both breast and ovarian cancer or with many cases of early-onset breast cancer, However, in an outbred population, the prevalence of BRCA1 and BRCA2 mutations in patients with breast cancer who were unselected for a family history of this disease has not been determined. Methods: Mutations in the BRCA1 and BRCA2 genes were detected in blood samples from two population-based series of young patients with breast cancer from Britain. Results: Mutations were detected in 15 (5.9%) of 254 women diagnosed with breast cancer before age 36 years (nine [3.5%] in BRCA1 and six [2.4%] in BRCA2) and in 15 (4.1%) of 363 women diagnosed from ages 36 through 45 years (seven [1.9%] in BRCA1 and eight [2.2%] in BRCA2). Eleven percent (six of 55) of patients with a first-degree relative who developed ovarian cancer or breast cancer by age 60 years were mutation carriers, compared with 45% (five of 11) of patients with two or more affected first- or second-degree relatives, The standardized incidence ratio for breast cancer in mothers and sisters was 365 (five observed and 1.37 expected) for 30 mutation carriers and 199 (64 observed and 32.13 expected) for 587 noncarriers. If we assume recent penetrance estimates, the respective proportions of BRCA1 and BRCA2, mutation carriers are 3.1% and 3.0%, respectively, of patients with breast cancer who are younger than age 50 years, 0.49% and 0.84% of patients with breast cancer who are age 50 years or older,,and 0.11% and 0.12% of women in the general population. Conclusions: Mutations in the BRCA1 and BRCA2 genes make approximately equal contributions to early-onset breast cancer in Britain and account for a small proportion of the familial risk of breast cancer.