Researchers from the Qatar Foundation have reported this week results from the first broad-based examination of cancer germline variation in diverse Middle East populations. The study published in the Lancet Oncology provides in-depth screening data of both common and rare cancer genetic markers in the Qatari population.
The new research will become an important tool to help create a national cancer prevention program in Qatar and highlight the diversity of disease-associated genetic markers, including of cancer, within Arab populations and the differences between these markers of disease and those of people with other ancestries.
“Incorporation of precision medicine technology, including cancer screening and genome sequencing, into the primary care system in Qatar has significant potential. 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,” said Lotfi Chouchane, lead principal investigator of the study and professor of Genetic Medicine, professor of Microbiology and Immunology at Weill Cornell Medicine–Qatar (WCM-Q).
“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. Our study is paving way to deliver a precision cancer prevention program in Qatar.”
The population sequencing effort comes as increased attention has been drawn to the significant variation of disease-causing variants among different ethnic populations, and the scarcity of genomic data from populations other than white northern European. As a result, disparities in genetic risk for cancer amongst various ancestry groups and populations remains poorly defined. It is more acute for Middle Eastern populations, where the paucity of genomic data could impact the potential of cancer genetic risk profiling and hamper the practice of precision oncology.
“The study—part of the Qatar Genome Program Research Consortium and among several other ongoing projects focusing on diseases of national priority—also aims to fill the gaps of the underrepresented Arab ancestry in genomic research and contribute to increase diversity and equity, a key aspect to advance science globally,” said Hamdi Mbarek, research partnerships manager at Qatar Genome Program.
To develop the new data set, the Qatar Genome Program collected DNA samples collected from 6,142 native Qataris, stratified into six distinct ancestry groups as general Arab, Persian, Arabian Peninsula, Admixture Arab, African, and South Asian. These samples underwent high-coverage genome sequencing which were then used to to develop polygenic risk scores (PRSs) for breast, prostate, and colorectal cancers—the most common cancers in Qatar. Training for the PRSs leveraged The Cancer Genome Atlas (TCGA) dataset, and their distributions were subsequently applied on the different genetic-ancestry groups of the Qatari population. Rare deleterious variants within 1,218 cancer-susceptibility genes were analyzed, and their clinical pathogenicity was assessed by ClinVar and the CharGer computational tool.
PRS analyses of the most common cancers in Qatar showed significant differences between the six ancestry groups (P<0.0001). Arabian Peninsula Qataris showed the lowest PRS average for colorectal cancer (PRS = -0.41), and those with an African origin showed the highest average for prostate cancer (PRS = 0.85).
Cancer-gene rare variant analysis identified 76 Qataris (1.24% of the 6,142 QGP individuals) carrying ClinVar pathogenic/likely pathogenic (P/LP) variants in clinically actionable cancer genes. CharGer predictions increased the total number of carriers to 195 individuals (3.17% of the cohort). Breast cancer pathogenic variants were over-represented in Qataris with a Persian origin (56.41% of the BRCA1/2 variant carriers) and completely absent in the Arabian Peninsula Qataris.
“We are determined at Qatar Genome Program, along with our partners, to spearhead the transition from bench to bedside, and these research findings are the starting point to provide a personalized screening for health and disease in Qatar and the region.” concluded Said Ismail, director of Qatar Genome Program.