BackgroundAs a large-scale study of Koreans, we evaluated the association between BRCA mutation and the prevalence of non-breast and ovary cancers in first- and second-degree relatives of high-risk breast cancer patients.MethodsWe organized familial pedigrees of 2555 patients with breast cancer who underwent genetic screening for BRCA1/2 in Samsung Medical Center between January 2002 and May 2018. Families with a member that had a history of cancer other than of the breast or ovary were regarded positive for other primary cancer.ResultsThe median age of the population was 40 years (range, 19 to 82 years). BRCA mutation was detected in 377 (14.8%) of the patients. The BRCA-positive group had a higher frequency of family history of breast or ovarian cancer (p < 0.001), bilateral breast cancer (p = 0.021), and the male gender (p = 0.038). There were 103 (27.3%) patients who had multiple risk factors in the BRCA-positive group, while there were 165 (7.6%) patients who had multiple risk factors in the BRCA-negative group (p < 0.001). BRCA mutation was detected in 215 (11.7%) of the 1841 families without history of other primary cancers. Among the 714 families with histories of other primary cancers, 162 (22.7%) had BRCA mutation, and this was significantly more frequent (p < 0.001) than in those without a history. The occurrence of other primary cancers in families of high-risk patients was associated with a younger age at diagnosis (p = 0.044), bilateral breast cancer (p = 0.006), and BRCA mutations (p < 0.001). The most common site for the occurrence of another type of primary cancer was the stomach. In the BRCA-positive group, the proportional incidences of stomach, pancreas, colorectal, lung, and uterine cancer were 13.8, 4.0, 7.7, 8.8, and 5.0%, respectively; these were all relatively higher than those in the BRCA-negative group.ConclusionsWe confirmed that BRCA mutation was associated with having multiple risk factors and an increased prevalence of non-breast and ovary cancers in first- and second-degree relatives of high-risk breast cancer patients. Due to the possibility of inherited cancer risk, genetic counseling with options for risk assessment and management should be provided to both patients and families of BRCA mutation carriers.

中文翻译：

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非乳腺癌和卵巢癌与高危乳腺癌患者一级和二级亲属的 BRCA 突变之间的关联：一项针对韩国人的大规模研究

背景作为一项针对韩国人的大规模研究，我们评估了 BRCA 突变与高危乳腺癌患者的一级和二级亲属中非乳腺癌和卵巢癌患病率之间的关联。方法我们组织了 2555 名乳腺癌患者的家族谱系。 2002 年 1 月至 2018 年 5 月期间在三星医疗中心接受 BRCA1/2 基因筛查的乳腺癌患者。家庭成员有除乳腺癌或卵巢癌以外的其他癌症病史，被认为对其他原发性癌症呈阳性。结果人口为 40 岁（范围为 19 至 82 岁）。在 377 名（14.8%）患者中检测到 BRCA 突变。BRCA 阳性组有更高的乳腺癌或卵巢癌家族史（p < 0.001）、双侧乳腺癌（p = 0.021）和男性（p = 0.038）。BRCA 阳性组有 103 名（27.3%）患者有多种危险因素，而 BRCA 阴性组有 165 名（7.6%）患者有多种危险因素（p < 0.001）。在没有其他原发性癌症病史的 1841 个家族中，有 215 个（11.7%）检测到 BRCA 突变。在有其他原发性癌症病史的 714 个家庭中，162 个（22.7%）有 BRCA 突变，这比没有病史的家庭更频繁（p < 0.001）。高危患者家族中其他原发性癌症的发生与诊断年龄较小（p = 0.044）、双侧乳腺癌（p = 0.006）和 BRCA 突变（p < 0.001）有关。另一种原发性癌症最常见的发生部位是胃。在 BRCA 阳性组中，胃的比例发生率，胰腺癌、结直肠癌、肺癌和子宫癌分别为 13.8%、4.0%、7.7%、8.8% 和 5.0%；这些都相对高于 BRCA 阴性组。结论我们证实，BRCA 突变与多种危险因素以及高危乳腺癌的一级和二级亲属中非乳腺癌和卵巢癌的患病率增加有关。癌症患者。由于遗传性癌症风险的可能性，应向患者和 BRCA 突变携带者家属提供风险评估和管理选项的遗传咨询。结论我们证实，BRCA 突变与多种危险因素有关，并与高危乳腺癌患者的一级和二级亲属中非乳腺癌和卵巢癌的患病率增加有关。由于遗传性癌症风险的可能性，应向患者和 BRCA 突变携带者家属提供风险评估和管理选项的遗传咨询。结论我们证实，BRCA 突变与多种危险因素有关，并且与高危乳腺癌患者的一级和二级亲属中非乳腺癌和卵巢癌的患病率增加有关。由于遗传性癌症风险的可能性，应向患者和 BRCA 突变携带者家属提供风险评估和管理选项的遗传咨询。