Investigation on the hereditary basis of colorectal cancers in an African population with frequent early onset cases
| العنوان: | Investigation on the hereditary basis of colorectal cancers in an African population with frequent early onset cases |
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| المؤلفون: | Simbarashe Rusakaniko, Dhiren Govender, Raj Ramesar, Leolin Katsidzira, Rudo Makunike-Mutasa, A. A. Vorster, Sandie R Thomson, Jonathan A. Matenga, Innocent T. Gangaidzo |
| المصدر: | PLoS ONE, Vol 14, Iss 10, p e0224023 (2019) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, Oncology, Molecular biology, Colorectal cancer, Mismatch Repair, Biochemistry, Geographical Locations, Sequencing techniques, 0302 clinical medicine, Medicine and Health Sciences, PMS2, DNA sequencing, Prospective Studies, Age of Onset, education.field_of_study, Multidisciplinary, Incidence, Genomics, Middle Aged, Epithelial Cell Adhesion Molecule, Prognosis, Lynch syndrome, 3. Good health, Nucleic acids, MutS Homolog 2 Protein, Genetic Diseases, 030220 oncology & carcinogenesis, Medicine, Female, Microsatellite Instability, 030211 gastroenterology & hepatology, Anatomy, Colorectal Neoplasms, MutL Protein Homolog 1, Transcriptome Analysis, Research Article, Next-Generation Sequencing, Zimbabwe, Adult, medicine.medical_specialty, Amsterdam criteria, Colon, Science, Population, DNA repair, Black People, MLH1, 03 medical and health sciences, Internal medicine, Genetics, medicine, Humans, Genetic Predisposition to Disease, education, Germ-Line Mutation, Colorectal Cancer, Clinical Genetics, Biology and life sciences, business.industry, Autosomal Dominant Diseases, Rectum, Cancers and Neoplasms, Computational Biology, Microsatellite instability, Hereditary Nonpolyposis Colorectal Cancer, DNA, Genome Analysis, medicine.disease, Research and analysis methods, Gastrointestinal Tract, Molecular biology techniques, Cross-Sectional Studies, MSH2, People and Places, Africa, business, Digestive System |
| الوصف: | BackgroundApproximately 25% of colorectal cancer patients in sub-Saharan Africa are younger than 40 years, and hereditary factors may contribute. We investigated the frequency and patterns of inherited colorectal cancer among black Zimbabweans.MethodsA population-based cross-sectional study of ninety individuals with a new diagnosis of colorectal cancer was carried out in Harare, Zimbabwe between November 2012 and December 2015. Phenotypic data was obtained using interviewer administered questionnaires, and reviewing clinical and pathology data. Cases were screened for mismatch repair deficiency by immunohistochemistry and/or microsatellite instability testing, and for MLH1, MSH2 and EPCAM deletions using multiplex ligation-dependent probe amplification. Next generation sequencing using a 16-gene panel was performed for cases with phenotypic features consistent with familial colorectal cancer. Variants were assessed for pathogenicity using the mean allele frequency, phenotypic features and searching online databases.ResultsThree Lynch syndrome cases were identified: MSH2 c.2634G>A pathogenic mutation, c.(1896+1_1897-1)_(*193_?)del , and one fulfilling the Amsterdam criteria, with MLH1 and PMS2 deficiency, but no identifiable pathogenic mutation. Two other cases had a strong family history of cancers, but the exact syndrome was not identified. The prevalence of Lynch syndrome was 3·3% (95% CI 0·7-9·4), and that of familial colorectal cancer was 5·6% (95% CI, 1·8-12·5).ConclusionsIdentifying cases of inherited colorectal cancer in sub-Saharan Africa is feasible, and our findings can inform screening guidelines appropriate to this setting. |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::75b8d76b838310bb8f2694b2b405da19Test https://doi.org/10.1371/journal.pone.0224023Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....75b8d76b838310bb8f2694b2b405da19 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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