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Large-scale cancer genetic analyses in the Middle East

A group of researchers at the Qatar Foundation have presented the first landscape of cancer genetic predisposition in the Middle East.

Cancer risk

Cancer development risk varies across different races, ethnicities and ancestries. Over the past decade, there has been an alarming increase in cancer rates in countries across the Middle East. In Qatar specifically, cancer is the second most prevalent non-communicable disease. This prevalence is expected to increase with population growth alongside an ageing population.

Many disease-associated gene variants show substantial diversity among different populations. However, the disparities in the genetic risk of cancer among different ancestry groups and populations remain poorly understood. Despite their diversity, Arabian populations have been missed from a lot of international genome or cancer consortia. Studying these populations could identify founder variants that influence the development or progression of cancer.

Genetic predisposition to cancer in Qatar

In a recent study, published in The Lancet Oncology, researchers used data from the Phase 1 cohort of the Qatar Genome Programme to explore genetic variation in cancer-susceptibility genes in the Qatari population. The programme specifically generated high-coverage genome sequencing on DNA samples collected from 6,142 native Qataris. These individuals were stratified into six distinct ancestry groups: general Arab, Persian, Arabian Peninsula, Admixture Arab, African, and South Asian.

The team evaluated the performance of polygenic risk scores (PRSs) for the most common cancers in Qatar. These included breast, prostate and colorectal cancers. The PRSs were trained using The Cancer Genome Atlas (TCGA) datasets and then were applied to the six different genetic ancestry groups. Rare deleterious variants within 1,218 cancer susceptibility genes were also analysed.

Whole genome sequencing quality control filtering cut the dataset down to 6,142 samples. PRS analyses of the most common cancer showed significant differences between the six ancestry groups (p<0.0001). Qataris with Arabian Peninsula ancestry showed the lowest PRS mean for colorectal cancer. Meanwhile, those of African ancestry showed the highest average for prostate cancer.

The team also identified 76 Qataris with ClinVar pathogenic or likely pathogenic variants in clinically actionable cancer genes. Variant analysis using CharGer also identified 195 individual carriers. Interestingly, pathogenic BRCA1/BRCA2 variants were over-represented in Qataris of Persian origin but completely absent in those of Arabian Peninsula origin.

Overall, these findings reveal a high degree of heterogeneity for cancer predisposition genes and PRSs across different ancestries from Qatar. This study provides important insights for cancer screening in the future and should be considered for implementing national cancer preventive medicine programmes.

Image credit: canva

More on these topics

Diversity / Equity / Population Genetics / WGS