NEW YORK — Genetic predisposition to cancer varies by ancestry within the Qatari population, a new analysis has found.
Using data generated through the Qatar Genome Programme, researchers applied existing polygenic risk scores for the three most common cancer types in Qatar: breast, colorectal, and prostate cancer. The program aims to generate sequencing and other data on the Qatari population with the eventual aim of enabling personalized medicine.
When the researchers determined these polygenic risk scores for their cohort, they noticed variations in risk based on individuals' ancestral backgrounds, suggesting cancer risk is not homogenous among Qataris. They further examined rare cancer-linked variants in program participants, finding that they, too, varied by ancestral background, as they reported in Lancet Oncology on Wednesday.
"With screening, prevention, and early detection at the forefront of the cancer agenda in Qatar, we propose to leverage the population genome sequencing by initiating national population testing programs to identify highly penetrant cancer gene mutation carriers, like individuals being at an increased risk for hereditary breast or ovarian cancers," senior author Lotfi Chouchane, a professor of genetic medicine, microbiology, and immunology at Weill Cornell Medicine – Qatar said in a statement. "Our study is paving the way to deliver a precision cancer prevention program in Qatar."
At the time of the analysis, the Qatar Genome Programme cohort included 6,218 individuals who underwent whole-genome sequencing. After filtering, the dataset included 6,142 individuals from six ancestry groups: general Arab, eastern or Persian, admixture of Arab subpopulations, Arabian peninsula, African, and South Asian.
Within this cohort, the researchers examined nine different existing polygenic risk scores for breast, colorectal, and prostate cancer and tested them to find the ones that performed the best in the Qatari population.
The polygenic risk scores pointed to differences in cancer risk between the six ancestry groups. Overall, individuals of general Arab ancestry had the lowest polygenic risk scores for breast cancer, while individuals with African ancestry had the highest polygenic risk scores for prostate cancer and those of Arabian Peninsula ancestry had the lowest polygenic risk scores for colorectal cancer.
This finding, the researchers noted, underscores how polygenic risk scores can vary, even in a small geographical location like Qatar.
Meanwhile, they found that 370 individuals in their cohort were carriers of clinically actionable or likely clinically actionable pathogenic or likely pathogenic cancer variants and noted that many of these variants were more common in the Qatar Genome Programme individuals than in public datasets. These included variants in EPCAM, MUTYH, BRCA1, and BRCA2.
Rare variants also varied in frequency by ancestral background. For instance, more than half of the BRCA1 and BRCA2 variant carriers were of Persian ancestry, while no pathogenic or likely pathogenic BRCA1 and BRCA2 variants were found among individuals of Arabian Peninsula origin. By contrast, Lynch syndrome-associated variants were overrepresented among individuals of Arabian Peninsula origin but did not appear among individuals of Persian ancestry.
Knowing how risk varies within the Qatari population could help efforts there to implement screening programs. "Incorporation of precision medicine technology, including cancer screening and genome sequencing, into the primary care system in Qatar has significant potential," Chouchane added. "The results of our study comprise a valuable source to capture cancer genetic markers in the different ancestries of the Arab populations and define quantitative and qualitative expectations for the results of personal genome sequencing."
The researchers noted that they were unable to validate that some variants they uncovered in their dataset were pathogenic in the cohort because of the limited number of individuals with cancer in the cohort. This, they added, points to the need to generate additional genomic and disease-related data within Middle Eastern populations.