lunes, 4 de noviembre de 2019

Investigation on the hereditary basis of colorectal cancers in an African population with frequent early onset cases. - PubMed - NCBI

2019 Oct 24;14(10):e0224023. doi: 10.1371/journal.pone.0224023. eCollection 2019.

Investigation on the hereditary basis of colorectal cancers in an African population with frequent early onset cases.

Katsidzira L1,2, Vorster A2,3, Gangaidzo IT1, Makunike-Mutasa R4, Govender D5, Rusakaniko S6, Thomson S7, Matenga JA1, Ramesar R2.

Author information

1: Department of Medicine, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe.
2: MRC/UCT Research Unit for Genomic and Precision Medicine, Division of Human Genetics, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
3: Central Analytical Facility (CAF), DNA Sequencing Unit, Stellenbosch University, Stellenbosch, South Africa.
4: Department of Histopathology, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe.
5: Division of Anatomical Pathology, Faculty of Health Sciences, University of Cape Town, and National Health Laboratory Service Groote Schuur hospital, Cape Town, South Africa.
6: Department of Community Medicine, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe.
7: Division of Gastroenterology, Department of Medicine, University of Cape Town, Cape Town, Groote Schuur Hospital, Cape Town, South Africa.

Abstract

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.