PDF(Pubmed)
Abstract：
Double pathogenic mutations occurring in an individual are considered a rare event. The introduction of a multiple-gene panel at Hong Kong Hereditary Breast Cancer Family Registry has allowed the identification of pathogenic variants in multiple genes, providing more information on clinical management and surveillance to the proband and their family members. Breast cancer patients who are double heterozygous (DH) for different hereditary breast and ovarian cancer syndrome (HBCO)-related genes were identified from a cohort of 3649 Chinese patients. Nine patients (0.25%) were observed to have germline DH mutations in ATM, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, MSH6, PALB2, and TP53. Three probands were diagnosed with unilateral breast cancer, two patients were diagnosed with bilateral breast cancer, and four patients had multiple primary cancers. The median age for breast cancer diagnosis was an early age of 36 years. Chinese DH carriers did not show worse phenotypes or have a significantly downhill clinical presentation. However, seven out of nine (77.8%) of our DH carriers harbored a BRCA1 mutation, and four of them (44.4%) developed bilateral breast cancer, suggesting Chinese DH individuals may have a higher chance of having bilateral breast cancer than other populations (p = 0.0237).
摘要：
个体中发生的双重致病性突变被认为是罕见事件。在香港遗传性乳腺癌家族注册中心引入多基因小组，可以识别多个基因的致病变异，向先证者及其家庭成员提供更多关于临床管理和监测的信息。从3649名中国患者队列中鉴定出具有不同遗传性乳腺癌和卵巢癌综合征（HBCO）相关基因的双杂合子（DH）的乳腺癌患者。观察到9名患者（0.25％）在ATM中具有种系DH突变，BRCA1、BRCA2、BRIP1、CDH1、CHEK2、MSH6、PALB2和TP53。三个先证者被诊断出患有单侧乳腺癌，两名患者被诊断为双侧乳腺癌，4名患者患有多原发癌。乳腺癌诊断的中位年龄为36岁。中国DH携带者没有表现出更差的表型或有明显的下坡临床表现。然而,九分之七（77.8%）的DH携带者携带BRCA1突变，其中4人(44.4%)发展为双侧乳腺癌,提示中国DH个体患双侧乳腺癌的几率可能高于其他人群(p=0.0237)。
