Genetic predisposition to cancer across people of different ancestries in Qatar: a population-based, cohort study

• Published in: The lancet oncology 2022-03, Vol.23 (3), p.341-352
• Main Authors: Saad, Mohamad, Mokrab, Younes, Halabi, Najeeb, Shan, Jingxuan, Razali, Rozaimi, Kunji, Khalid, Syed, Najeeb, Temanni, Ramzi, Subramanian, Murugan, Ceccarelli, Michele, Rafii Tabrizi, Arash, Bedognetti, Davide, Chouchane, Lotfi
• Format: Article
• Language: English
• Subjects: Biobanks; BRCA1 protein; BRCA2 protein; Breast cancer; Cohort analysis; Cohort Studies; Colorectal cancer; Colorectal carcinoma; Computer applications; Datasets; Disease; DNA sequencing; Genes; Genetic diversity; Genetic Predisposition to Disease; Genomes; Genomics; Health risk assessment; Humans; Male; Neoplasms - epidemiology; Neoplasms - genetics; Oncogenes; Ovarian cancer; Pathogenicity; Population; Population studies; Population-based studies; Precision medicine; Prostate; Prostate cancer; Qatar - epidemiology; Quality control; Whole genome sequencing
• ISSN: 1470-2045; 1474-5488
• DOI: 10.1016/S1470-2045(21)00752-X

Disparities in the genetic risk of cancer among various ancestry groups and populations remain poorly defined. This challenge is even more acute for Middle Eastern populations, where the paucity of genomic data could affect the clinical potential of cancer genetic risk profiling. We used data from the phase 1 cohort of the Qatar Genome Programme to investigate genetic variation in cancer-susceptibility genes in the Qatari population. The Qatar Genome Programme generated high-coverage genome sequencing on DNA samples collected from 6142 native Qataris, stratified into six distinct ancestry groups: general Arab, Persian, Arabian Peninsula, Admixture Arab, African, and South Asian. In this population-based, cohort study, we evaluated the performance of polygenic risk scores for the most common cancers in Qatar (breast, prostate, and colorectal cancers). Polygenic risk scores were trained in The Cancer Genome Atlas (TCGA) dataset, and their distributions were subsequently applied to the six different genetic ancestry groups of the Qatari population. Rare deleterious variants within 1218 cancer susceptibility genes were analysed, and their clinical pathogenicity was assessed by ClinVar and the CharGer computational tools. The cohort included in this study was recruited by the Qatar Biobank between Dec 11, 2012, and June 9, 2016. The initial dataset comprised 6218 cohort participants, and whole genome sequencing quality control filtering led to a final dataset of 6142 samples. Polygenic risk score analyses of the most common cancers in Qatar showed significant differences between the six ancestry groups (p