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

Leolin Katsidzira,Raj Ramesar,Dhiren Govender,Anna Vorster,Simbarashe Rusakaniko,Jonathan A Matenga,Rudo Makunike-Mutasa,Innocent T Gangaidzo,Sandie Thomson,Alvaro Galli

doi:10.1371/journal.pone.0224023

Abstract

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.

Highlights

The incidence of colorectal cancer is gradually rising in some countries in sub-Saharan Africa, including Kenya, Nigeria, and Zimbabwe.[1]
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
It has been hypothesised that the frequency of hereditary colorectal cancers, Lynch syndrome, is high in sub-Saharan Africa.[7]

Summary

Introduction

The incidence of colorectal cancer is gradually rising in some countries in sub-Saharan Africa, including Kenya, Nigeria, and Zimbabwe.[1]. 1 in 4 individuals with colorectal cancer in sub-Saharan Africa is under the age of 40 years.[1] In general, young people with colorectal cancer are more likely to have a pathogenic germline mutation.[5, 6] it has been hypothesised that the frequency of hereditary colorectal cancers, Lynch syndrome, is high in sub-Saharan Africa.[7] This is supported by the high frequency of histological features associated with Lynch syndrome (mucinous and signet ring cell morphology), and of mismatch repair protein deficiency in colorectal cancers in this region.[7,8,9] The earlier age of onset of colorectal cancer among African-Americans provides additional, indirect evidence of an intrinsic genetic predisposition among people of African ancestry.[10]. 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.

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