Systematic Review of Genetic Factors in the Etiology of Esophageal Squamous Cell Carcinoma in African Populations

Frontiers in Genetics

Hannah Simba¹  Vikash Sewram¹  Gerard Tromp³  Vittoria Lutje⁴  Helena Kuivaniemi⁶ 

[1] African Cancer Institute, Division of Health Systems and Public Health, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa;Bioinformatics Unit, South African Tuberculosis Bioinformatics Initiative, Stellenbosch University, Cape Town, South Africa;Centre for Bioinformatics and Computational Biology, Stellenbosch University, Stellenbosch, South Africa;Cochrane Infectious Diseases Group, Liverpool, United Kingdom;DST–NRF Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Cape Town, South Africa;Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa;South African Medical Research Council Centre for Tuberculosis Research, Stellenbosch University, Cape Town, South Africa;

关键词: esophageal squamous cell carcinoma;    genetic association;    somatic variant;    germline mutation;    sequence variants;    systematic review;   

DOI  :  10.3389/fgene.2019.00642

来源: DOAJ

【 摘 要 】

Background: Esophageal squamous cell carcinoma (ESCC), one of the most aggressive cancers, is endemic in Sub-Saharan Africa, constituting a major health burden. It has the most divergence in cancer incidence globally, with high prevalence reported in East Asia, Southern Europe, and in East and Southern Africa. Its etiology is multifactorial, with lifestyle, environmental, and genetic risk factors. Very little is known about the role of genetic factors in ESCC development and progression among African populations. The study aimed to systematically assess the evidence on genetic variants associated with ESCC in African populations.Methods: We carried out a comprehensive search of all African published studies up to April 2019, using PubMed, Embase, Scopus, and African Index Medicus databases. Quality assessment and data extraction were carried out by two investigators. The strength of the associations was measured by odds ratios and 95% confidence intervals.Results: Twenty-three genetic studies on ESCC in African populations were included in the systematic review. They were carried out on Black and admixed South African populations, as well as on Malawian, Sudanese, and Kenyan populations. Most studies were candidate gene studies and included DNA sequence variants in 58 different genes. Only one study carried out whole-exome sequencing of 59 ESCC patients. Sample sizes varied from 18 to 880 cases and 88 to 939 controls. Altogether, over 100 variants in 37 genes were part of 17 case-control genetic association studies to identify susceptibility loci for ESCC. In these studies, 25 variants in 20 genes were reported to have a statistically significant association. In addition, eight studies investigated changes in cancer tissues and identified somatic alterations in 17 genes and evidence of loss of heterozygosity, copy number variation, and microsatellite instability. Two genes were assessed for both genetic association and somatic mutation.Conclusions: Comprehensive large-scale studies on the genetic basis of ESCC are still lacking in Africa. Sample sizes in existing studies are too small to draw definitive conclusions about ESCC etiology. Only a small number of African populations have been analyzed, and replication and validation studies are missing. The genetic etiology of ESCC in Africa is, therefore, still poorly defined.

【 授权许可】

Unknown