163 High Incidence of Early Onset Colon Cancer in Ethiopia: Clinical and Therapeutic Evaluation With Genetic Mutational Analyses

Abstract

INTRODUCTION: Colon cancer has been reported to occur early in certain African regions, but the understanding of genetic modifications leading to early disease is incomplete. We aimed to study cases of early colon cancer and genetic modifications leading to these tumors in Ethiopia. METHODS: We evaluated all colon masses detected between 2015 and 2018 at Black Lion Hospital, Addis Ababa. Clinical, endoscopic and pathology descriptions were assessed for all cases in 30-year-olds or younger. Subsets of pathology block-tissues were evaluated for genetic modifications via Multiplex Ligation-dependent Probe Amplification. RESULTS: A total of 38 cases of colon cancer ages 30 or earlier were identified. These represented 13% of all cases of colon cancer in the 3-year period. The median age was 27 years (IQR 27–30), and 50% of individuals were female. None of the cases reported a family history of colon cancer or had evidence of inflammatory bowel disease (IBD). The most common presenting symptom was rectal bleeding (57%) followed by a change in bowel habit (22%). All but one sample were identified as adenocarcinoma, 78% were confined to the rectum, and 65% had distant metastasis or locally advanced disease at the time of diagnosis. Longer duration of symptoms correlated with the presence of metastasis on diagnosis (P = 0.035). Surgery (23%) and chemotherapy (15%) were the most frequently used treatments. We performed genetic analysis of biopsy tissue in a subset of 3 individuals: a) 21 y/o-male showed decrease copies of APC, increase in K-ras, v600f mutation in BRAF and decrease in MSH2 and MLH1; b) 21 y/o-female showed duplication of exon 4 APC, decrease in K-ras and decreased copies of MSH-2; c) 30 y/o-female showed decreased copies of APC, decreased copies of K-ras and BRAF and decreased copies of MSH2 and MLH1. CONCLUSION: We report a high incidence of early colon cancer in Ethiopia with no family history or IBD. Most patients presented with rectal bleeding. Genetic analyses in a subset of patients showed APC and K-ras alterations as well as modifications of mismatch repair pathways.