Importance of multigene panel test in patients with consanguineous marriage and family history of breast cancer

Ozmen,Vahit; Caglayan,Ahmet Okay; Yararbas,Kanay; Ordu,Cetin; Aktepe,Fatma; Ozmen,Tolga; Ilgun,Ahmet Serkan; Soybir,Gursel; Alco,Gul; Tsaousis,Georgios N.; Papadopoulou,Eirini; Agiannitopoulos,Konstantinos; Pepe,Georgia; Kampouri,Stavroula; Nasioulas,George; Sezgin,Efe; Soran,Atilla

doi:10.3892/ol.2022.13238

Importance of multigene panel test in patients with consanguineous marriage and family history of breast cancer

Authors:
- Vahit Ozmen
- Ahmet Okay Caglayan
- Kanay Yararbas
- Cetin Ordu
- Fatma Aktepe
- Tolga Ozmen
- Ahmet Serkan Ilgun
- Gursel Soybir
- Gul Alco
- Georgios N. Tsaousis
- Eirini Papadopoulou
- Konstantinos Agiannitopoulos
- Georgia Pepe
- Stavroula Kampouri
- George Nasioulas
- Efe Sezgin
- Atilla Soran
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Affiliations: Department of Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul 34093, Turkey, Department of Medical Genetics, Dokuz Eylul University, Izmir 35330, Turkey, Department of Medical Genetics, Demiroglu Bilim University, Istanbul 34403, Turkey, Department of Medical Oncology, Demiroglu Bilim University, Istanbul 34403, Turkey, Department of Pathology, Memorial Hospital, Istanbul 34385, Turkey, Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33127, USA, Department of Surgery, Demiroglu Bilim University, Istanbul 34403, Turkey, Department of Surgery, Memorial Hospital, Istanbul 34385, Turkey, Department of Radiation Oncology, Demiroglu Bilim University, Istanbul 34403, Turkey, Genekor Medical SA, Athens 15344, Greece, Department of Food Engineering, Faculty of Engineering, Izmir Institute of Technology, Izmir 35430, Turkey, Department of Surgical Oncology, University of Pittsburgh, Pittsburgh, PA 15260, USA
Published online on: February 9, 2022 https://doi.org/10.3892/ol.2022.13238
Article Number: 118
Copyright: © Ozmen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Next‑generation sequencing (NGS) technology is used to evaluate hereditary cancer risks of patients worldwide; however, information concerning the germline multigene mutational spectrum among patients with breast cancer (BC) with consanguineous marriage (CM) is limited. Therefore, this prospective study aimed to determine the molecular characteristics of patients with BC who were tested with multigene hereditary cancer predisposition NGS panel and to show the effect of CM on cancer‑related genes. Patients with BC with or without CM and family history (FH) of BC treated in our breast center were selected according to The National Comprehensive Cancer Network (NCCN) criteria for hereditary BC. In these patients, the analysis of a panel of 33 genes involved in hereditary cancer predisposition was performed after genetic counseling by using NGS. The pathogenic variant (PV) and the variant of uncertain significance (VUS) were found to be 15.8 and 47.4%, respectively. PVs were identified in 10/33 genes in 34 patients; 38.2% in BRCA1/2 genes; 6, 24, and 14% in other high, moderate and low‑risk genes, respectively. The CM rate was 17.7% among the 215 patients with BC. The PV rate was 13.2% in patients with CM and 16.4% in patients without CM (P=0.80). When PV and VUS were evaluated together, the PV+VUS ratio was significantly higher in patients with CM and FH of BC than patients without CM and FH of BC (88.2 vs. 63.3%, P=0.045). Analysis of multigene panel provided 9.76% additional PVs in moderate/low‑risk genes. The PV rate was similar in patients with BC with or without CM. A high PV+VUS ratio in patients with CM and FH of BC suggests that genes whose importance are unknown are likely to be pathogenic genes later.

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