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

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.

Practical approach to the prevention of preeclampsia: from screening to pharmaceutical intervention.

Preeclampsia occurs in 3-8% of the pregnancies and is associated with a high rate of morbi-mortality, both for mothers and the fetus. Screening and prevention of patients at risk are the optimal way to reduce the morbi-mortality of this disease. To set-up a preventive approach to preeclampsia (PE), one has to identify using a screening strategy for the population at risk and propose them an appropriate therapeutic intervention that would bear a favorable benefits/risk ratio. While the classical method only considers epidemiological risk factors to set up preventive measures, several authors have set-up complex multiparameter algorithm to detect a population at risk of PE. The new pyramid of pregnancy care integrates an early clinic allowing the assessment of biophysical and biochemical markers combined with maternal factors. Such an approach can identify pregnancies that are at high risk of PE and reduce its prevalence using low-aspirin regimen initiated as early as possible in the population at risk.

Skin trophicity improvement by mechanotherapy for lipofilling-based breast reconstruction postradiation therapy.

BACKGROUND: Post-mastectomy irradiation severely impairs skin trophicity resulting in poor prosthetic implant outcome. Autologous fat grafting improves skin quality allowing minimally invasive approach with prosthetic reconstruction. Here, we report our pilot experience of preoperative mechanotherapy to optimize lipofilling and subsequent prosthetic reconstruction outcome. METHODS: We retrospectively included 65 women that had breast reconstruction using autologous fat grafting and implant placement from 2012 to 2018 benefiting or not from mechanotherapy before the reconstructive procedure. Demographic and surgical outcomes were recorded. RESULTS: The volume of fat injected was significantly superior in the mechanotherapy group compared with the controls for the first and second lipofilling (259.3 mL vs 150.6 mL and 251.8 mL vs 154 mL, respectively). Sixteen patients among controls required a pre-expansion prosthesis compared with none in the endermology group. The prosthesis volume was smaller in the endermology group. Six patients in the endermology group had a reconstruction without prosthesis. The aesthetic score evaluated by patients was 4.8 with no statistically significant difference between the two groups. CONCLUSION: Preoperative skin mechanotherapy and postoperative skin mechanotherapy increase skin compliance. It is associated with a higher volume of fat injection and lower prosthesis volume. If confirmed in a prospective study, endermology could become a standard in patients' preparation for lipofilling-based reconstruction.