Hereditary Breast and Ovarian Cancer (HBOC) and Lynch Syndrome (LS) are the most common inherited cancer syndromes identified with genetic testing. Testing, though, commonly reveals variants of uncertain significance (VUSs). This is a retrospective observational study designed to determine the prevalence of pathogenic mutations and VUSs in patients tested for HBOC and/or LS and to explore the characteristics of the VUS population. Patients 18–80 years old that met NCCN criteria for HBOC and/or LS genetic screening were tested between 2006 and 2020 at Mount Auburn Hospital in Cambridge, Massachusetts. A total of 663 patients were included in the study, with a mean age of 50 years old and 90% being females. Pathogenic mutations were identified in 12.5% and VUSs in 28.3%. VUS prevalence was associated with race (p-value = 0.019), being particularly higher in Asian populations. Patients with a personal history of breast cancer or family history of breast or ovarian cancer were more likely to have a VUS (personal breast: OR: 1.55; CI: 1.08–2.25; family breast: OR: 1.68; CI: 1.08–2.60, family ovarian OR: 2.29; CI: 1.04–5.45). In conclusion, VUSs appear to be detected in almost one third patients tested for cancer genetic syndromes, and thus future work is warranted to determine their significance in cancer development.
遗传性乳腺癌和卵巢癌综合征（HBOC）和林奇综合征（LS）是通过基因检测识别出的最常见的遗传性癌症综合征。然而，检测常发现意义未明的变异（VUSs）。本研究为回顾性观察性研究，旨在确定接受HBOC和/或LS检测患者中致病性突变和VUSs的流行率，并探讨VUS人群的特征。研究对象为2006年至2020年间在马萨诸塞州剑桥市奥本山医院接受检测、符合美国国家综合癌症网络（NCCN）HBOC和/或LS基因筛查标准的18-80岁患者。研究共纳入663名患者，平均年龄50岁，其中90%为女性。致病性突变检出率为12.5%，VUSs检出率为28.3%。VUS流行率与种族相关（p值=0.019），在亚洲人群中尤为显著。有个人乳腺癌病史或家族乳腺癌/卵巢癌病史的患者更可能携带VUS（个人乳腺癌史：OR：1.55；CI：1.08-2.25；家族乳腺癌史：OR：1.68；CI：1.08-2.60；家族卵巢癌史：OR：2.29；CI：1.04-5.45）。综上所述，近三分之一接受癌症遗传综合征检测的患者可检出VUSs，因此未来有必要进一步研究其在癌症发生发展中的意义。
肿瘤(癌症)患者之家