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Investigation on the hereditary basis of colorectal cancers in an African population with frequent early onset cases
BACKGROUND: Approximately 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. METHODS: A population-based cross-sectional study of...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812839/ https://www.ncbi.nlm.nih.gov/pubmed/31647837 http://dx.doi.org/10.1371/journal.pone.0224023 |
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author | Katsidzira, Leolin Vorster, Anna Gangaidzo, Innocent T. Makunike-Mutasa, Rudo Govender, Dhiren Rusakaniko, Simbarashe Thomson, Sandie Matenga, Jonathan A. Ramesar, Raj |
author_facet | Katsidzira, Leolin Vorster, Anna Gangaidzo, Innocent T. Makunike-Mutasa, Rudo Govender, Dhiren Rusakaniko, Simbarashe Thomson, Sandie Matenga, Jonathan A. Ramesar, Raj |
author_sort | Katsidzira, Leolin |
collection | PubMed |
description | BACKGROUND: Approximately 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. METHODS: A 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. RESULTS: Three 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). CONCLUSIONS: Identifying cases of inherited colorectal cancer in sub-Saharan Africa is feasible, and our findings can inform screening guidelines appropriate to this setting. |
format | Online Article Text |
id | pubmed-6812839 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-68128392019-11-02 Investigation on the hereditary basis of colorectal cancers in an African population with frequent early onset cases Katsidzira, Leolin Vorster, Anna Gangaidzo, Innocent T. Makunike-Mutasa, Rudo Govender, Dhiren Rusakaniko, Simbarashe Thomson, Sandie Matenga, Jonathan A. Ramesar, Raj PLoS One Research Article BACKGROUND: Approximately 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. METHODS: A 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. RESULTS: Three 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). CONCLUSIONS: Identifying cases of inherited colorectal cancer in sub-Saharan Africa is feasible, and our findings can inform screening guidelines appropriate to this setting. Public Library of Science 2019-10-24 /pmc/articles/PMC6812839/ /pubmed/31647837 http://dx.doi.org/10.1371/journal.pone.0224023 Text en © 2019 Katsidzira et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Katsidzira, Leolin Vorster, Anna Gangaidzo, Innocent T. Makunike-Mutasa, Rudo Govender, Dhiren Rusakaniko, Simbarashe Thomson, Sandie Matenga, Jonathan A. Ramesar, Raj Investigation on the hereditary basis of colorectal cancers in an African population with frequent early onset cases |
title | Investigation on the hereditary basis of colorectal cancers in an African population with frequent early onset cases |
title_full | Investigation on the hereditary basis of colorectal cancers in an African population with frequent early onset cases |
title_fullStr | Investigation on the hereditary basis of colorectal cancers in an African population with frequent early onset cases |
title_full_unstemmed | Investigation on the hereditary basis of colorectal cancers in an African population with frequent early onset cases |
title_short | Investigation on the hereditary basis of colorectal cancers in an African population with frequent early onset cases |
title_sort | investigation on the hereditary basis of colorectal cancers in an african population with frequent early onset cases |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812839/ https://www.ncbi.nlm.nih.gov/pubmed/31647837 http://dx.doi.org/10.1371/journal.pone.0224023 |
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