Research Papers:

Investigating the prevalence of pathogenic variants in Saudi Arabian patients with familial cancer using a multigene next generation sequencing panel

Musa AlHarbi, Nahla Ali Mobark, Wael Abdel Rahman AlJabarat, Hadeel ElBardis, Ebtehal AlSolme, Abdullah Bany Hamdan, Ali H. AlFakeeh, Fatimah AlMushawah, Fawz AlHarthi, Abdullah A. AlSharm, Ali Abdullah O. Balbaid, Naji AlJohani, Alicia Y. Zhou, Heather A. Robinson, Saleh A. Alqahtani and Malak Abedalthagafi _

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Oncotarget. 2023; 14:580-594. https://doi.org/10.18632/oncotarget.28457

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Musa AlHarbi1, Nahla Ali Mobark1, Wael Abdel Rahman AlJabarat1, Hadeel ElBardis2, Ebtehal AlSolme2, Abdullah Bany Hamdan3, Ali H. AlFakeeh1, Fatimah AlMushawah4, Fawz AlHarthi2, Abdullah A. AlSharm3, Ali Abdullah O. Balbaid2, Naji AlJohani5, Alicia Y. Zhou6, Heather A. Robinson7, Saleh A. Alqahtani8,9 and Malak Abedalthagafi2,10

1 Department of Pediatric Oncology, Comprehensive Cancer Centre, King Fahad Medical City, Riyadh, Saudi Arabia

2 Genomics Research Department, King Fahad Medical City, Riyadh, Saudi Arabia

3 Department of Oncology, King Fahad Medical City, Riyadh, Saudi Arabia

4 Department of Surgery, King Fahad Medical City, Riyadh, Saudi Arabia

5 Department of Medicine, King Fahad Medical City, Riyadh, Saudi Arabia

6 Color Health Inc., Burlingame, CA 94010, USA

7 Health eResearch Centre, University of Manchester, Manchester, UK

8 Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD 21287, USA

9 Liver Transplant Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

10 Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, GA 30322, USA

Correspondence to:

Malak Abedalthagafi, email: [email protected]

Keywords: cancer; hereditary cancer syndrome; genetic counseling; NGS; cancer screening

Received: March 16, 2023     Accepted: June 01, 2023     Published: June 12, 2023

Copyright: © 2023 AlHarbi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Family history is an important factor in determining hereditary cancer risk for many cancer types. The emergence of next-generation sequencing (NGS) has expedited the discovery of many hereditary cancer susceptibility genes and the development of rapid, affordable testing kits. Here, a 30-gene targeted NGS panel for hereditary cancer risk assessment was tested and validated in a Saudi Arabian population. A total of 310 subjects were screened, including 57 non-cancer patients, 110 index patients with cancer and 143 of the cancer patients’ family members, 16 of which also had cancer. Of the 310 subjects, 119 (38.4%) were carriers of pathogenic or likely pathogenic variants (PVs) affecting one or more of the following genes: TP53, ATM, CHEK2, CDH1, CDKN2A, BRCA1, BRCA2, PALB2, BRIP1, RAD51D, APC, MLH1, MSH2, MSH6, PMS2, PTEN, NBN/NBS1 and MUTYH. Among 126 patients and relatives with a history of cancer, 49 (38.9%) were carriers of PVs or likely PVs. Two variants in particular were significantly associated with the occurrence of a specific cancer in this population (APC c.3920T>A – colorectal cancer/Lynch syndrome (p = 0.026); TP53 c.868C>T; – multiple colon polyposis (p = 0.048)). Diverse variants in BRCA2, the majority of which have not previously been reported as pathogenic, were found at higher frequency in those with a history of cancer than in the general patient population. There was a higher background prevalence of genetic variants linked to familial cancers in this cohort than expected based on prevalence in other populations.

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