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

Abstract

PURPOSE Colon cancer has been reported to occur early in certain African regions, but our understanding of the genetic modifications that lead to early disease is incomplete. We aimed to study cases of early colon cancer and the 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, Ethiopia. Clinical, endoscopic, and pathology descriptions were assessed for all cases in patients age 30 years or younger. Subsets of pathology block tissues were evaluated for genetic modifications via multiplex ligation-dependent probe amplification. RESULTS We identified a total of 38 cases of colon cancer in patients age 30 years or younger. These represented 13% of all cases of colon cancer in the 3-year period. Median age was 27 years (interquartile range, 27-30 years), and 50% of individuals were female. None of the cases reported a family history of colon cancer or had evidence of inflammatory bowel disease. The most common presenting symptom was rectal bleeding (57%), followed by a change in bowel habit (22%). All samples but one 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 = .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-year-old male showed decreased copies of APC, an increase in K-ras, V600F mutation in BRAF, and a decrease in MSH2 and MLH1; a 21-year-old female showed duplication of exon 4 APC, a decrease in K-ras, and decreased copies of MSH-2; and a 30-year-old 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 in patients with no family history or inflammatory bowel disease. Genetic analyses in a subset of patients showed APC and K-ras alterations as well as modifications of the mismatch repair pathway.