Kwong Ava, Ho Cecilia Y S, Au Chun-Hang, Ma Edmond S K
Department of Surgery, The University of Hong Kong, Hong Kong SAR, China.
Department of Surgery, Hong Kong Sanatorium & Hospital, Hong Kong SAR, China.
Cancers (Basel). 2024 Jul 15;16(14):2547. doi: 10.3390/cancers16142547.
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 , , , , , , , , and . 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 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 ( = 0.0237).
个体中出现的双重致病突变被认为是罕见事件。香港遗传性乳腺癌家族登记处引入的多基因检测面板能够识别多个基因中的致病变异，为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名中国患者队列中识别出了不同遗传性乳腺癌和卵巢癌综合征（HBCO）相关基因的双杂合（DH）乳腺癌患者。观察到9名患者（0.25%）在、、、、、、、和中有胚系DH突变。3名先证者被诊断为单侧乳腺癌，2名患者被诊断为双侧乳腺癌，4名患者有多个原发性癌症。乳腺癌诊断的中位年龄为36岁，属早年发病。中国的DH携带者并未表现出更差的表型或明显恶化的临床表现。然而，我们9名DH携带者中有7名（77.8%）携带突变，其中4名（44.4%）患双侧乳腺癌，这表明中国的DH个体患双侧乳腺癌的几率可能高于其他人群（P = 0.0237）。
