Elmetnawy Wafaa, Nader Heba, ElNahas Tamer, Sabet Salwa, Bassiony Heba, ElNahass Yasser
Department of Clinical Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Department of Zoology, Faculty of Science, Cairo University, Cairo, Egypt.
Sci Rep. 2025 Jul 18;15(1):26067. doi: 10.1038/s41598-025-09810-5.
The rising incidence of breast cancer (BC) among Egyptian females with a mortality rate of 11% and younger age at diagnosis implied the study of the interplay of BRCA gene variants with other BC risk factors. The study enrolled 500 BC Egyptian females with a mean age of 47.29 ± 13.26 years for whom BRCA1/2 testing was offered. A history of BC and/or other related cancer was recorded for all patients. Peripheral blood samples were obtained for genomic DNA extraction in view of germline BRCA gene testing on the MiSeq platform. A positive family history was reported in 352 patients (70.4%). Patients with hormone receptor-positive (HR+) BC constituted 195 cases (39%) cases, while 305 patients (61%) had hormone receptor-negative (HR-) BC. Among the HR- group, 268 patients (53%) had triple-negative BC (TNBC), and 37 patients had low estrogen receptor (ER) (1-10%) and/ or low progesterone receptor (PR) expression with HER2 negative status. Patients with HER2-positive BC were excluded from the enrollment and directed to specific targeted therapy. Variants were classified according to the American College of Medical Genetics (ACMG) and the Association for Molecular Pathology (AMP) criteria. Carriers of gBRCA1/2 PVs/LPVs were 58 patients (11.6%) of whom 34 (6.8%) had BRCA1 PVs/LPVs and 24 (4.8%) had BRCA2 PVs/LPVs. Patients with TNBC demonstrated a higher rate of gBRCA1/2 PVs/LPVs (17.5%). We recorded 55 PVs/LPVs in both genes, 44 single nucleotide variants (SNVs), and 11 copy number variations (CNVs). Three novel gBRCA1 LPVs; c.2791del, c.361G>T and c.4431dup and two novel gBRCA2 LPVs; gBRCA2 c.3139del and c.5690 dup were identified. Variants of uncertain significance (VUS) were found in 22 patients, of whom 13 (59%) had a positive family history of breast/ovarian cancer. Genomic testing for BRCA1/2 status as part of a routine BC diagnostic workup contributes to comprehensive BC risk assessment.Trial registration: Egyptian National Cancer Institute IRB approval number: 2301-305-051. Date of registration: 24th Jan 2023.
在埃及女性中，乳腺癌（BC）的发病率不断上升，死亡率为11%，且诊断年龄较轻，这意味着需要研究BRCA基因变异与其他BC风险因素之间的相互作用。该研究招募了500名埃及BC女性，平均年龄为47.29±13.26岁，并为她们提供了BRCA1/2检测。记录了所有患者的BC病史和/或其他相关癌症病史。鉴于要在MiSeq平台上进行种系BRCA基因检测，采集了外周血样本用于基因组DNA提取。352名患者（70.4%）报告有阳性家族史。激素受体阳性（HR+）BC患者有195例（39%），而305名患者（61%）为激素受体阴性（HR-）BC。在HR-组中，268名患者（53%）为三阴性乳腺癌（TNBC），37名患者雌激素受体（ER）低表达（1-10%）和/或孕激素受体（PR）低表达且HER2阴性。HER2阳性BC患者被排除在研究之外，并接受特定的靶向治疗。变异根据美国医学遗传学学会（ACMG）和分子病理学协会（AMP）的标准进行分类。gBRCA1/2致病性变异/可能致病性变异携带者有58名患者（11.6%），其中34名（6.8%）有BRCA1致病性变异/可能致病性变异，24名（4.8%）有BRCA2致病性变异/可能致病性变异。TNBC患者的gBRCA1/2致病性变异/可能致病性变异发生率更高（17.5%）。我们在两个基因中记录了55个致病性变异/可能致病性变异、44个单核苷酸变异（SNV）和11个拷贝数变异（CNV）。鉴定出3个新的gBRCA1可能致病性变异：c.2791del、c.361G>T和c.4431dup，以及2个新的gBRCA2可能致病性变异：gBRCA2 c.3139del和c.5690 dup。在22名患者中发现了意义未明的变异（VUS），其中13名（59%）有乳腺癌/卵巢癌阳性家族史。作为常规BC诊断检查的一部分进行BRCA1/2状态的基因组检测有助于全面的BC风险评估。试验注册：埃及国家癌症研究所IRB批准号：2301-305-051。注册日期：2023年1月24日。
