Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Eur J Cancer. 2013 Jun;49(9):2101-6. doi: 10.1016/j.ejca.2013.02.018. Epub 2013 Mar 13.
Risk estimates for proven non-carriers in BRCA mutation families are inconsistent for breast cancer and lacking for ovarian cancer. We aimed to assess the age-related risks for breast and ovarian cancer for proven non-carriers in these families.
A consecutive cohort study ascertained 464 proven non-carriers who had a first-degree relative with a pathogenic BRCA mutation. Kaplan-Meier analyses were used to estimate the age-related cancer risks, and we calculated standardised incidence ratios.
In the 464 non-carriers, 17 breast cancers and two ovarian cancers were detected at a mean age of 47 years (95% confidence interval (CI) 32-61) and 49 years (95% CI 32-67), respectively. Overall, by the age of 50, the breast and ovarian cancer risks among non-carriers were 6.4% (95% CI 2.9-9.8%) and 0.4% (95% CI 0-1.3%), of which the breast cancer risk was statistically significantly higher than the risk in the general population. In particular, the number of breast cancers among non-carriers in BRCA1 families was higher than expected for the general population (standardised incidence ratio (SIR) 2.0, 95% CI 1.1-3.3). In the BRCA1 cohort, the mean number of breast cancer cases was higher in families in which non-carriers were diagnosed before the age of 50 (p=0.04).
The age at diagnosis of breast cancer in non-carriers in BRCA mutation families is younger than expected, yielding an increased risk in the fifth decade. This effect is most evident in BRCA1 families. If our results are confirmed by others, this could affect the advice given on breast cancer screening to proven non-carriers between the age of 40 and 50 in such families.
BRCA 突变家族中已证实的非携带者的乳腺癌和卵巢癌风险估计值不一致，且缺乏后者的风险估计值。我们旨在评估这些家族中已证实的非携带者的乳腺癌和卵巢癌相关年龄风险。
一项连续队列研究确定了 464 名具有致病性 BRCA 突变一级亲属的已证实非携带者。采用 Kaplan-Meier 分析估计与年龄相关的癌症风险，并计算标准化发病比。
在 464 名非携带者中，17 例乳腺癌和 2 例卵巢癌分别在 47 岁（95%置信区间（CI）32-61）和 49 岁（95%CI 32-67）的平均年龄时被检出。总体而言，在 50 岁之前，非携带者的乳腺癌和卵巢癌风险分别为 6.4%（95%CI 2.9-9.8%）和 0.4%（95%CI 0-1.3%），其中乳腺癌风险显著高于普通人群。特别是，BRCA1 家族中，非携带者的乳腺癌病例数高于普通人群预期（标准化发病比（SIR）为 2.0，95%CI 1.1-3.3）。在 BRCA1 队列中，非携带者在 50 岁之前被诊断的家族中，乳腺癌的平均病例数更高（p=0.04）。
BRCA 突变家族中，非携带者的乳腺癌诊断年龄比预期年轻，导致在第五个十年风险增加。这种影响在 BRCA1 家族中最为明显。如果其他研究结果证实了我们的结果，这可能会影响此类家族中 40 至 50 岁之间已证实的非携带者的乳腺癌筛查建议。
