Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history:: A combined analysis of 22 studies
Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history:: A combined analysis of 22 studies
复制标题
DOI：
10.1086/375033
复制
发表时间：
2003-05-01
影响因子：
9.8
通讯作者：
Easton, DF
中科院分区：
文献类型：
--
作者：
Antoniou, A;Pharoah, PDP;Easton, DF
BRCA1和BRCA2的种系突变会导致乳腺癌和卵巢癌的高风险，但这些风险的平均大小是不确定的，可能取决于具体情况。基于多病例家系的估计可能会丰富更高风险和/或其他家族性风险因素的突变，而基于未被选为家族史的病例的研究的风险估计一直不准确。我们汇集了22项研究的家系数据，涉及8,139名未被选为家族史的指标病例，其中女性(86%)或男性(2%)乳腺癌或上皮性卵巢癌(12%)，其中500人已被发现携带BRCA1或BRCA2的种系突变。根据突变携带者的亲属中乳腺癌和卵巢癌的发生情况，采用改进的分离分析方法估计突变携带者的乳腺癌和卵巢癌发病率。BRCA1突变携带者70岁时患乳腺癌的平均累积风险为65%(95%可信区间为44%-78%)，患卵巢癌的平均累积风险为39%(18%-54%)。BRCA2的相应估计为45%(31%-56%)和11%(2.4%-19%)。在BRCA1突变携带者中，乳腺癌的相对风险随着年龄的增长而显著下降(P趋势.0012)，但对于BRCA2突变携带者来说，这一趋势并不显著。根据诊断的乳腺癌病例指数，携带者的风险更高
Germline mutations in BRCA1 and BRCA2 confer high risks of breast and ovarian cancer, but the average magnitude of these risks is uncertain and may depend on the context. Estimates based on multiple-case families may be enriched for mutations of higher risk and/or other familial risk factors, whereas risk estimates from studies based on cases unselected for family history have been imprecise. We pooled pedigree data from 22 studies involving 8,139 index case patients unselected for family history with female (86%) or male (2%) breast cancer or epithelial ovarian cancer (12%), 500 of whom had been found to carry a germline mutation in BRCA1 or BRCA2. Breast and ovarian cancer incidence rates for mutation carriers were estimated using a modified segregation analysis, based on the occurrence of these cancers in the relatives of mutation-carrying index case patients. The average cumulative risks in BRCA1-mutation carriers by age 70 years were 65% (95% confidence interval 44%-78%) for breast cancer and 39% (18%-54%) for ovarian cancer. The corresponding estimates for BRCA2 were 45% (31%-56%) and 11% (2.4%-19%). Relative risks of breast cancer declined significantly with age for BRCA1-mutation carriers ( P trend .0012) but not for BRCA2-mutation carriers. Risks in carriers were higher when based on index breast cancer cases diagnosed at