Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases. Anglian Breast Cancer Study Group.
Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases. Anglian Breast Cancer Study Group.
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DOI：
10.1054/bjoc.2000.1407
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发表时间：
2000-11
影响因子：
8.8
通讯作者：
Anglian Breast Cancer Study Group
中科院分区：
文献类型：
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作者：
Anglian Breast Cancer Study Group
对 BRCA1 和 BRCA2 对近亲繁殖群体中乳腺癌发病率的贡献的估计是基于小型研究或选择了早期诊断病例的研究。其中只有一个报告了与这些基因突变相关的乳腺癌风险的估计，并且没有发表基于人群的病例系列得出的卵巢癌风险估计。我们对 55 岁之前诊断出的一系列基于人群的乳腺癌病例进行了 BRCA1 和 BRCA2 突变筛查。突变携带者的谱系信息用于估计外显率以及 BRCA1 和 BRCA2 导致的乳腺癌家族风险比例。我们在 1220 例乳腺癌病例中确定了 8 名 (0.7%) BRCA1 和 16 名 (1.3%) BRCA2 突变携带者（根据 15% 聚合酶链反应失败率调整后的实际样本量为 1435）。在 35 岁之前诊断的病例中，并且随着患有乳腺癌或卵巢癌的亲属数量的增加，突变患病率要高得多。然而，大多数突变携带者是在年龄较大的人群中被诊断出来的，少数人报告其一级亲属患有乳腺癌。据估计，BRCA1 突变携带者到 80 岁时乳腺癌外显率为 48%（95% CI 7-82%），BRCA2 突变携带者为 74%（7-94%）。到 80 岁时，BRCA1 和 BRCA2 的卵巢癌外显率合计为 22% (6-65%)。 17% 的乳腺癌家族风险归因于 BRCA1 和 BRCA2。出生时，BRCA1 突变携带者的估计患病率为 0.07% 或 0.09%，具体取决于用于计算的外显率函数。对于 BRCA2，出生率估计为 0.14% 和 0.22%。 BRCA1 和 BRCA2 基因突变在人群中很少见，并且仅占英国所有乳腺癌的一小部分。他们占乳腺癌家族风险的不到五分之一。基于家族史和发病年龄的 BRCA1 和 BRCA2 突变检测资格标准只能识别出一小部分突变携带者。 © 2000 年癌症研究活动
Estimates of the contribution of BRCA1 and BRCA2 to breast cancer incidence in outbred populations have been based on studies that are either small or have selected for cases diagnosed at an early age. Only one of these has reported an estimate of the breast cancer risk associated with a mutation in these genes, and there is no published ovarian cancer risk estimate derived from a population-based case series. We screened a population-based series of breast cancer cases diagnosed before the age of 55 for mutations in BRCA1 and BRCA2. Pedigree information from the mutation carriers was used to estimate penetrance and the proportion of familial risk of breast cancer due to BRCA1 and BRCA2. We identified eight (0.7%)BRCA1 and 16 (1.3%)BRCA2 mutation carriers in 1220 breast cancer cases (actual sample size 1435 adjusted for 15% polymerase chain reaction failure rate). Mutation prevalence was substantially higher in cases diagnosed before 35 years-of-age and with increasing number of relatives affected with breast or ovarian cancer. However, most mutation carriers were diagnosed in the older age groups, and a minority reported a first-degree relative with breast cancer. Breast cancer penetrance by age 80 was estimated to be 48% (95% CI 7–82%) for BRCA1 mutation carriers and 74% (7–94%) for BRCA2 mutation carriers. Ovarian cancer penetrance for BRCA1 and BRCA2 combined was 22% (6–65%) by age 80. 17% of the familial risk of breast cancer was attributable to BRCA1 and BRCA2. At birth, the estimated prevalence of BRCA1 mutation carriers was 0.07% or 0.09% depending on the penetrance function used for the calculation. For BRCA2 the birth prevalence estimates were 0.14% and 0.22%. Mutations in the genes BRCA1 and BRCA2 are rare in the population and account for a small fraction of all breast cancer in the UK. They account for less than one fifth of the familial risk of breast cancer. Eligibility criteria for BRCA1 and BRCA2 mutation testing based on family history and age of onset will identify only a small proportion of mutation carriers. © 2000 CancerResearch Campaign