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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.)

Colorectal cancer is preventable and treatable by screening and early detection. Fecal immunochemical tests (FIT) for average risk individuals is an effective strategy for screening. Incidence and mortality in Mexico is increasing and large-scale screening programs do not yet exist. The aim of this study was to evaluate the feasibility of FIT-based colorectal cancer screening program in Mexico City. For more than 15 months, average risk individuals in Mexico City were invited to participate at Mexico's Instituto Nacional de Cancerologia (INCan, Mexico City, Mexico). Participants received an FIT kit for stool collection, results ≥20 ng/mL were referred for high quality colonoscopy. Participants' results were classified according to the most advanced clinical finding as: adenocarcinoma, high-risk adenomas, low-risk adenomas, serrated lesions, hyperplastic polyps, and no polyps. Sequential analyses were performed to assess the positive predictive value (PPV) of FIT. A total of 810 participants were eligible, 737 (91.0%) returned the FIT and 112 (15.2%) had an abnormal result. Of these participants, 87 (77.7%) completed colonoscopy. Clinical findings of participants included: seven (8.1%) adenocarcinomas, 18 (20.7%) high-risk adenomas, 23 (26.4%) low-risk adenomas, one (1.2%) serrated lesions, 14 (16.1%) hyperplasic polyps, and 24 (27.6%) no polyps. The PPV of FIT using the ≥20 ng/mL was 8.1% for cancer and 20.7% for high-risk adenomas. In conclusion, colorectal cancer screening with FIT is feasible at INCan in Mexico City, where resources are available. Further studies are needed to determine feasibility of colorectal cancer screening in other settings, as well as optimal hemoglobin detection cut-off points to maximize the population benefits of colorectal cancer screening with FIT in Mexico., (©2020 American Association for Cancer Research.)

Background: Diet is associated with colorectal cancer survival. Yet, adherence to nutrition guidelines is low among colorectal cancer survivors., Methods: We conducted a pilot trial among colorectal cancer survivors to evaluate a 12-week remote dietary intervention. Participants received print materials and were randomized (1:1) to intervention (website, text messages) or wait-list control. Primary outcomes included feasibility and acceptability. We also explored change in diet from 0 to 12 and 24 weeks and change from 0 to 12 weeks in anthropometry and circulating biomarkers (Trial Registration: NCT02965521)., Results: We randomized 50 colorectal cancer survivors (25 intervention, 25 control). Retention was 90% at 12 weeks and 84% at 24 weeks. Participants had a median age of 55 years and were 66% female, 70% non-Hispanic white, and 96% had a college degree. The intervention arm responded to a median 15 (71%) of 21 text messages that asked for a reply [interquartile range (IQR) = 8, 19] and visited the website a median of 13 (15%) days (IQR = 1, 33) of the 84 study days., Conclusions: We developed a Web-based dietary intervention for colorectal cancer survivors. Our pilot results suggest that colorectal cancer survivors may engage more with text messages than a study website. Research to improve tailoring of text messages, while maintaining scalability, is needed., Impact: Remote dietary interventions using text messages may be feasible for colorectal cancer survivors. See all articles in this CEBP Focus section, "Modernizing Population Science.", (©2020 American Association for Cancer Research.)

Unlabelled: Patients with pancreatic and biliary carcinomas lack personalized treatment options, in part because biopsies are often inadequate for molecular characterization. Cell-free DNA (cfDNA) sequencing may enable a precision oncology approach in this setting. We attempted to prospectively analyze 54 genes in tumor and cfDNA for 26 patients. Tumor sequencing failed in 9 patients (35%). In the remaining 17, 90.3% (95% confidence interval, 73.1%-97.5%) of mutations detected in tumor biopsies were also detected in cfDNA. The diagnostic accuracy of cfDNA sequencing was 97.7%, with 92.3% average sensitivity and 100% specificity across five informative genes. Changes in cfDNA correlated well with tumor marker dynamics in serial sampling (r = 0.93). We demonstrate that cfDNA sequencing is feasible, accurate, and sensitive in identifying tumor-derived mutations without prior knowledge of tumor genotype or the abundance of circulating tumor DNA. cfDNA sequencing should be considered in pancreatobiliary cancer trials where tissue sampling is unsafe, infeasible, or otherwise unsuccessful., Significance: Precision medicine efforts in biliary and pancreatic cancers have been frustrated by difficulties in obtaining adequate tumor tissue for next-generation sequencing. cfDNA sequencing reliably and accurately detects tumor-derived mutations, paving the way for precision oncology approaches in these deadly diseases., (©2015 American Association for Cancer Research.)