Molecular screening for Lynch syndrome in early-onset colorectal cancer in Northern Tanzania.

Colorectal cancer (CRC) incidence is increasing in sub-Saharan Africa, with a growing burden of early-onset disease and advanced-stage presentation. The contribution of Lynch syndrome (LS), the most common hereditary cause of CRC, remains poorly defined in this region. We conducted a retrospective pilot study among patients aged ≤50 years diagnosed with CRC in northern Tanzania to determine the prevalence of LS. Tumour samples were initially screened for mismatch repair (MMR) deficiency using immunohistochemistry and microsatellite instability (MSI) testing. Cases demonstrating MMR protein loss underwent MLH1 promoter hypermethylation analysis, and those without hypermethylation were subsequently selected for germline sequencing of MMR genes. Among 47 patients, six (12.8%) had MSI-high tumours and three (6.4%) carried pathogenic germline variants consistent with LS. The observed prevalence is comparable to reports from high-income countries and other African cohorts. These findings demonstrate that LS contributes meaningfully to early-onset CRC in Tanzania and support the need to expand molecular diagnostics and hereditary cancer screening in resource-limited settings.