Brose Marcia S, Rebbeck Timothy R, Calzone Kathleen A, Stopfer Jill E, Nathanson Katherine L, Weber Barbara L
Department of Medicine and Abramson Family Cancer Research Institute, University of Pennsylvania Cancer Center, Philadelphia 19104, USA.
J Natl Cancer Inst. 2002 Sep 18;94(18):1365-72. doi: 10.1093/jnci/94.18.1365.
Increasing numbers of BRCA1 mutation carriers are being identified in cancer risk evaluation programs. However, no estimates of cancer risk specific to a clinic-based population of mutation carriers are available. These data are clinically relevant, because estimates based on families ascertained for linkage studies may overestimate cancer risk in mutation carriers, and population-based series may underestimate it. Wide variation in risk estimates from these disparate ascertainment groups makes counseling in risk evaluation programs difficult. The purpose of this study was to estimate BRCA1-related cancer risks for individuals ascertained in a breast cancer risk evaluation clinic.
Cumulative observed and age-adjusted cancer risk estimates were determined by analyzing 483 BRCA1 mutation carriers in 147 families identified in two academic breast and ovarian cancer risk evaluation clinics. Cancer risks were computed from the proportion of individuals diagnosed with cancer during a 10-year age interval from among the total number of individuals alive and cancer-free at the beginning of that interval. Age-of-diagnosis comparisons were made using two-sided Student's t tests.
By age 70, female breast cancer risk was 72.8% (95% confidence interval [CI] = 67.9% to 77.7%) and ovarian cancer risk was 40.7% (95% CI = 35.7% to 45.6%). The risk for a second primary breast cancer by age 70 was 40.5% (95% CI = 34.1% to 47.0%). We also identified an increased risk of cancer of the colon (twofold), pancreas (threefold), stomach (fourfold), and fallopian tube (120-fold) in BRCA1 mutation carriers as compared with Surveillance, Epidemiology, and End Results (SEER) Program population-based estimates.
The estimates for breast and ovarian cancer risk in BRCA1 mutation carriers is higher than population-based estimates but lower than estimates based on families ascertained for linkage studies. These cancer risk estimates may most closely approximate those faced by BRCA1 mutation carriers identified in risk evaluation clinics.
在癌症风险评估项目中，越来越多的BRCA1突变携带者被识别出来。然而，目前尚无针对基于临床的突变携带者群体的癌症风险估计数据。这些数据具有临床相关性，因为基于连锁研究确定的家系得出的估计可能高估了突变携带者的癌症风险，而基于人群的系列研究可能低估了这一风险。这些不同确定群体的风险估计差异很大，给风险评估项目的咨询工作带来了困难。本研究的目的是估计在乳腺癌风险评估诊所确定的个体中与BRCA1相关的癌症风险。
通过分析在两家学术性乳腺癌和卵巢癌风险评估诊所确定的147个家系中的483名BRCA1突变携带者，确定累积观察到的和年龄调整后的癌症风险估计值。癌症风险是根据在一个10年年龄区间内被诊断患有癌症的个体比例计算得出的，该比例是相对于该区间开始时存活且无癌症的个体总数而言的。使用双侧学生t检验进行诊断年龄比较。
到70岁时，女性乳腺癌风险为72.8%（95%置信区间[CI]=67.9%至77.7%），卵巢癌风险为40.7%（95%CI=35.7%至45.6%）。到70岁时，第二原发性乳腺癌的风险为40.5%（95%CI=34.1%至47.0%）。与监测、流行病学和最终结果（SEER）项目基于人群的估计相比，我们还发现BRCA1突变携带者患结肠癌（两倍）、胰腺癌（三倍）、胃癌（四倍）和输卵管癌（120倍）的风险增加。
BRCA1突变携带者的乳腺癌和卵巢癌风险估计高于基于人群的估计，但低于基于连锁研究确定的家系的估计。这些癌症风险估计可能最接近在风险评估诊所确定的BRCA1突变携带者所面临的风险。
