Search

Background: Esophageal squamous cell carcinoma (ESCC) comprises 90% of all esophageal cancer cases globally and is the most common histology in low-resource settings. Eastern Africa has a disproportionately high incidence of ESCC., Methods: We describe the genomic profiles of 61 ESCC cases from Tanzania and compare them to profiles from an existing cohort of ESCC cases from Malawi. We also provide a comparison to ESCC tumors in The Cancer Genome Atlas (TCGA)., Results: We observed substantial transcriptional overlap with other squamous histologies via comparison with TCGA PanCan dataset. DNA analysis revealed known mutational patterns, both genome-wide as well as in genes known to be commonly mutated in ESCC. TP53 mutations were the most common somatic mutation in tumors from both Tanzania and Malawi but were detected at lower frequencies than previously reported in ESCC cases from other settings. In a combined analysis, two unique transcriptional clusters were identified: a proliferative/epithelial cluster and an invasive/migrative/mesenchymal cluster. Mutational signature analysis of the Tanzanian cohort revealed common signatures associated with aging and cytidine deaminase activity (APOBEC) and an absence of signature 29, which was previously reported in the Malawi cohort., Conclusions: This study defines the molecular characteristics of ESCC in Tanzania, and enriches the Eastern African dataset, with findings of overall similarities but also some heterogeneity across two unique sites., Impact: Despite a high burden of ESCC in Eastern Africa, investigations into the genomics in this region are nascent. This represents the largest comprehensive genomic analysis ESCC from sub-Saharan Africa to date., (©2023 American Association for Cancer Research.)

Background: East Africa is affected by a disproportionately high burden of esophageal squamous cell carcinoma (ESCC)., Methods: We conducted an incident case-control study in Dar es Salaam, Tanzania with 1:1 matching for gender and age. A questionnaire evaluated known and putative risk factors for ESCC. Cochran-Mantel-Haenszel and multivariable conditional logistic regression analyses were applied to evaluate associations with ESCC risk, with adjustment for geographic zone., Results: Of 471 cases and 471 controls, the majority were male (69%); median ages were 59 and 55, respectively. In a multivariable logistic regression model, a low International Wealth Index (IWI) score [OR 2.57; 95% confidence interval (CI), 1.41-4.68], former smoking (OR 2.45; 95% CI, 1.46-4.13), second-hand smoke in the household (OR 1.67; 95% CI, 1.01-2.77), daily spicy chilies (OR 1.62; 1.04-2.52), and daily salted foods (OR 2.02; 95% CI, 1.06-3.85) were associated with increased risk of ESCC. Daily consumption of raw greens (OR 0.36; 95% CI, 0.16-0.80), fruit (OR 0.47; 95% CI, 0.27-0.82), and smoked fish (OR 0.31; 95% CI, 0.15-0.66) were protective. Permanent residence in the Central (OR 5.03; 95% CI, 2.16-11.73), Northern-Lake (OR 2.40; 95% CI, 1.46-3.94), or Southern Highlands zones (OR 3.18; 95% CI, 1.56-6.50) of Tanzania were associated with increased risk compared with residence in the Eastern zone., Conclusions: Low IWI score, smoke exposure(s), geographic zone, and dietary factors were associated with risk for ESCC in Tanzania., Impact: These findings will inform the development of future hypothesis-driven studies to examine risk factors for the high burden of ESCC in East Africa. See related commentary by McCormack et al., p. 248 ., (©2020 American Association for Cancer Research.)