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Introduction: Colorectal cancer is the third most common cancer and the second most common cause of cancer mortality worldwide. There are disparities in the epidemiology of colorectal cancer across different populations, most probably due to differences in exposure to lifestyle and environmental factors related to colorectal cancer. In the next decade, East Africa is predicted to face an unprecedented growth of cancers, including colorectal cancer. There are indications of a significant burden of late-stage and aggressive colorectal cancer in the Ugandan population. Survival rates in SubSaharan Africa remain poor, with Uganda registering a low 3-year overall survival of 33.3%. There is a paucity of data on colorectal cancer molecular subtypes and their characteristics among patients in East Africa. Objective: The objective is to determine the prevalence of colorectal cancer molecular subtypes among Ugandan colorectal cancer patients. Methodology: A descriptive cross-sectional study was conducted in two referral hospitals and two missionary hospitals in Uganda. Data was obtained on demographics, topography of tumour and stage. The histopathological subtype, grade and LVI status of CRC were obtained from H&E slides. Immunohistochemistry was carried out to determine whether PMS2 and MLH1 were MMR-deficient or proficient. CRC formalin-fixed paraffin-embedded (FFPE) tissue blocks were used to extract DNA. The MLH-1, MSH2, MSH6, BRAF and KRAS genes were sequenced using NGS sequencing, and the CIMP status was obtained using targeted NextGen Bisulphite sequencing (tNGBS). The tumour molecular subtypes were defined according to the Jass classification: Type 1: MSI positive, CIMP-positive, BRAF-mutated (positive), K-ras mutation negative; Type 2: MSS (MSI negative), CIMP-positive, BRAF-mutated (positive), Kras-mutation (negative); Type 3: MSS (MSI negative), CIMP-negative, BRAF-mutation negative, Kras mutated (positive); Type 4: MSS (MSI negative), CIMP-negative, BRAF-mutation negative, Kras-mutation negative.; Type 5: MSI positive, CIMP-negative, BRAF mutation-negative, Kras-mutation negative (Lynch syndrome). Other marker combinations were grouped together as “other category”. Categorical data were summarised using proportions and frequencies corresponding to the MSI status and each of the five molecular subtypes defined using the Jass classification. Categorical and continuous variables were analysed using the Chi-square and Fisher’s exact tests. For all the analyses, a p-value ≤0.05 was considered statistically significant. Results: Out of 127 CRC patients, the median (IQR) age was 54(43-67) years. Advanced stage III+IV was found in 109(85.8%) cases. Poorly differentiated tumours constituted 14(11.02%), moderately differentiated 96(75.6%) and well differentiated 17(13.4%). There were 52(40.9%) MSI positive tumours and 75(59.06%) MSS tumours. The molecular subtypes defined by the Jass classification included 0% type I, 2.3% type 2, 3.3% type 3, 45.7% type 4, and 38.0% type 5 (Lynch syndrome). Colorectal cancer patients with Lynch syndrome have a pathogenic germline variant in one MMR gene and a secondary gene inactivation due to promoter hypermethylation or loss of heterozygosity. Conclusions: Importantly, sporadic MSI-high/CIMP-high tumours (Jass type 1) were not present (0%), and BRAF/KRAS pathogenic mutations were infrequent, unlike tumours from the Western world. Many young CRC participants presented with poorly differentiated and advanced-stage tumours, with MSI-positive tumours mainly due to Lynch syndrome. Immunohistochemistry, MSI testing and colonoscopic surveillance are cheaper than germline testing, and in Uganda may be carried out on CRC patients with MSI-positive histology.