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

• Published in: Oncotarget Vol. 14; no. 1; pp. 580 - 594
• Main Authors: AlHarbi, Musa, Mobark, Nahla Ali, AlJabarat, Wael Abdel Rahman, ElBardis, Hadeel, AlSolme, Ebtehal, Hamdan, Abdullah Bany, AlFakeeh, Ali H, AlMushawah, Fatimah, AlHarthi, Fawz, AlSharm, Abdullah A, Balbaid, Ali Abdullah O, AlJohani, Naji, Zhou, Alicia Y, Robinson, Heather A, Alqahtani, Saleh A, Abedalthagafi, Malak
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 12.06.2023
• Subjects: Colorectal Neoplasms; Genetic Predisposition to Disease; High-Throughput Nucleotide Sequencing; Humans; Nasopharyngeal Neoplasms; Prevalence; Research Paper; Saudi Arabia; Saudi Arabia; genetic counseling; hereditary cancer syndrome; cancer; cancer screening; NGS
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.28457

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: and . 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 ( = 0.026); c.868C>T; - multiple colon polyposis ( = 0.048)). Diverse variants in 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.