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

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

Lancet Oncol

Genetic Intelligence Laboratory, Weill Cornell Medicine-Qatar, Doha, Qatar; Department of Genetic Medicine, Weill Cornell Medicine, New York, NY, USA; Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA. Electronic address:

Published: March 2022

AI Article Synopsis

  • The study investigates genetic risk factors for cancer within the Qatari population, focusing on disparities among different ancestry groups due to limited genomic data for Middle Eastern populations.
  • The Qatar Genome Programme collected DNA samples from 6142 native Qataris, which were analyzed for polygenic risk scores related to common cancers such as breast, prostate, and colorectal cancers, revealing significant differences among six ancestry groups.
  • Findings indicate that ancestry impacts cancer risk, with individuals from the Arabian Peninsula showing the lowest risk for colorectal cancer and those of African descent displaying the highest risk for prostate cancer, alongside the identification of rare genetic variants linked to cancer susceptibility.

Article Abstract

Background: 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.

Methods: 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.

Findings: 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<0·0001). Qataris with Arabian Peninsula ancestry showed the lowest polygenic risk score mean for colorectal cancer (-0·41), and those of African ancestry showed the highest average for prostate cancer (0·85). Cancer-gene rare variant analysis identified 76 Qataris (1·2% of 6142 individuals in the Qatar Genome Programme cohort) carrying ClinVar pathogenic or likely pathogenic variants in clinically actionable cancer genes. Variant analysis using CharGer identified 195 individuals carriers (3·17% of the cohort). Breast cancer pathogenic variants were over-represented in Qataris of Persian origin (22 [56·4%] of 39 BRCA1/BRCA2 variant carriers) and completely absent in those of Arabian Peninsula origin.

Interpretation: We observed a high degree of heterogeneity for cancer predisposition genes and polygenic risk scores across ancestries in this population from Qatar. Stratification systems could be considered for the implementation of national cancer preventive medicine programmes.

Funding: Qatar Foundation.

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Source
http://dx.doi.org/10.1016/S1470-2045(21)00752-XDOI Listing

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