Peto J, Collins N, Barfoot R, Seal S, Warren W, Rahman N, Easton D F, Evans C, Deacon J, Stratton M R
Section of Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK.
J Natl Cancer Inst. 1999 Jun 2;91(11):943-9. doi: 10.1093/jnci/91.11.943.
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.
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.
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.
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.
在大多数同时患有乳腺癌和卵巢癌或有许多早发性乳腺癌病例的家族中发现了BRCA1和BRCA2基因的突变。然而，在一个远交群体中，未因该疾病家族史而被挑选的乳腺癌患者中BRCA1和BRCA2突变的患病率尚未确定。
在来自英国的两个基于人群的年轻乳腺癌患者系列的血样中检测BRCA1和BRCA2基因的突变。
在254名36岁之前被诊断为乳腺癌的女性中，有15名（5.9%）检测到突变（BRCA1中有9名[3.5%]，BRCA2中有6名[2.4%]）；在363名36至45岁被诊断为乳腺癌的女性中，有15名（4.1%）检测到突变（BRCA1中有7名[1.9%]，BRCA2中有8名[2.2%]）。在60岁前有患卵巢癌或乳腺癌的一级亲属的患者中，11%（55名中的6名）是突变携带者，相比之下，有两名或更多受影响的一级或二级亲属的患者中，45%（11名中的5名）是突变携带者。30名突变携带者的母亲和姐妹中乳腺癌的标准化发病比为365（观察到5例，预期1.37例），587名非携带者的标准化发病比为199（观察到64例，预期32.13例）。如果我们假设近期的外显率估计值，那么在50岁以下的乳腺癌患者中，BRCA1和BRCA2突变携带者的比例分别为3.1%和3.0%，在50岁及以上的乳腺癌患者中分别为0.49%和0.84%，在普通人群中的女性中分别为0.11%和0.12%。
在英国，BRCA1和BRCA2基因的突变对早发性乳腺癌所起的作用大致相同，且在乳腺癌家族风险中所占比例较小。
