Park Kyung-Sun, Lee Woochang, Seong Moon-Woo, Kong Sun-Young, Lee Kyung-A, Ha Jung-Sook, Cho Eun-Hae, Han Sung-Hee, Park Inho, Kim Jong-Won
Department of Laboratory Medicine, Kyung Hee University School of Medicine and Kyung Hee University Medical Center, Seoul 02447, Korea.
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
Cancers (Basel). 2021 May 2;13(9):2192. doi: 10.3390/cancers13092192.
In this study, we performed a comprehensive analysis of / variants and associated cancer risk in Korean patients considering two aspects: variants of uncertain significance (VUS) and pathogenic or likely pathogenic variants (PLPVs) in and . This study included 5433 Korean participants who were tested for genes. The variants were classified following the standards/guidelines for interpretation of genetic variants and using a multifactorial probability-based approach. In Korea, 15.8% of participants had or PLPVs. To estimate the additional sample numbers needed to resolve unclassified status, we applied a simulation analysis. The simulation study for VUS showed that the smaller the number of samples, the more the posterior probability was affected by the prior probability; in addition, more samples for VUS than those of VUS were required to resolve the unclassified status, and the presence of clinical information associated with their VUS was an important factor. The cumulative lifetime breast cancer risk was 59.1% (95% CI: 44.1-73.6%) for and 58.3% (95% CI: 43.2-73.0%) for carriers. The cumulative lifetime ovarian cancer risk was estimated to be 36.9% (95% CI: 23.4-53.9%) for and 14.9% (95% CI: 7.4-28.5%) for carriers.
在本研究中，我们从两个方面对韩国患者的/变体及相关癌症风险进行了全面分析：不确定意义的变体（VUS）以及和中的致病或可能致病变体（PLPVs）。本研究纳入了5433名接受基因检测的韩国参与者。这些变体依据遗传变体解读的标准/指南并采用基于多因素概率的方法进行分类。在韩国，15.8%的参与者携带或PLPVs。为估计解决未分类状态所需的额外样本数量，我们进行了模拟分析。对VUS的模拟研究表明，样本数量越少，后验概率受先验概率的影响就越大；此外，解决未分类状态需要的VUS样本比VUS的样本更多，并且与VUS相关的临床信息的存在是一个重要因素。对于携带者，累积终生乳腺癌风险为59.1%（95%CI：44.1 - 73.6%），对于携带者为58.3%（95%CI：43.2 - 73.0%）。对于携带者，累积终生卵巢癌风险估计为36.9%（95%CI：23.4 - 53.9%），对于携带者为14.9%（95%CI：7.4 - 28.5%）。
