Pócza Tímea, Papp János, Bozsik Anikó, Grolmusz Vince Kornél, Nagy Petra, Patócs Attila, Butz Henriett
Department of Molecular Genetics and the National Tumor Biology Laboratory, National Institute of Oncology, 1122 Budapest, Hungary.
HUN-REN-OOI-TTK-HCEMM Oncogenomics Research Group, 1052 Budapest, Hungary.
Int J Mol Sci. 2025 Aug 29;26(17):8390. doi: 10.3390/ijms26178390.
Identification of two or more pathogenic/likely pathogenic (P/LP) variants in cancer susceptibility genes carried by the same patient have important consequences for patient management. We have limited information about the effect of double heterozygosity (DH) in cancer susceptibility genes. The prevalence of DH among Hungarian cancer patients referred to oncogenetic counselling, and comparison of their phenotypes to single variant carriers were performed. In total, 2050 patients were analysed by multigene panel sequencing. Variants of 48 established cancer predisposition genes by ACMG guidelines were evaluated. In overall, P/LP variants were found in 19.8% of cases. DH was observed in 16 cases, amount to 0.8% of all patients, and to 4.0% of positive cases. Appearance of multiple primary tumours was not associated with DH compared to non-P/LP and single P/LP carriers ( = 0.71 and = 0.54, respectively). Within a cohort of patients referred with suspected HBOC syndrome, earlier tumour formation was observed when DH cases were compared to non-P/LP carriers ( = 0.01), but difference between single and DH carriers was not statistically significant ( = 0.19; Bonferroni corrected alpha = 0.017). Our observations provide information about the incidence of DH status among Hungarian hereditary cancer patients and suggest that DH did not increase the risk of cancer compared to individuals with single P/LP mutation.
在同一名患者携带的癌症易感基因中鉴定出两个或更多致病/可能致病（P/LP）变异对患者管理具有重要意义。我们对癌症易感基因中的双重杂合性（DH）效应了解有限。我们对转诊至肿瘤遗传咨询的匈牙利癌症患者中DH的患病率进行了研究，并将他们的表型与单变异携带者进行了比较。总共对2050名患者进行了多基因panel测序分析。根据ACMG指南评估了48个已确定的癌症易感基因的变异。总体而言，在19.8%的病例中发现了P/LP变异。在16例患者中观察到DH，占所有患者的0.8%，占阳性病例的4.0%。与非P/LP和单P/LP携带者相比，多发原发性肿瘤的出现与DH无关（分别为 = 0.71和 = 0.54）。在一组疑似遗传性乳腺癌卵巢癌综合征（HBOC）的患者中，将DH病例与非P/LP携带者进行比较时，观察到更早的肿瘤形成（ = 0.01），但单变异携带者和DH携带者之间的差异无统计学意义（ = 0.19；Bonferroni校正α = 0.017）。我们的观察结果提供了匈牙利遗传性癌症患者中DH状态发生率的信息，并表明与单P/LP突变个体相比，DH不会增加患癌风险。
