Abstract 6221: Gastric atrophy is associated with increased risk of esophageal squamous cell carcinoma in Lilongwe, Malawi

Background: Esophageal cancer (EC) is the 7th leading cause of cancer worldwide, with nearly 500,000 annual deaths. Esophageal squamous cell carcinoma (ESCC), the most prevalent subtype, has high incidence in East Asia, South and East Africa. Malawi has the highest EC incidence rate, almost exclusively ESCC, with risk factors including tobacco use, hot beverages, fuel source, moldy grain consumption, geophagia, poor oral health, and possibly HIV. H. pylori’s role in ESCC is unclear, with adverse, null, and protective effects across different populations. Gastric atrophy, a potential result of H. pylori infection, may increase ESCC risk by promoting gastrointestinal bacterial overgrowth that exposes esophageal mucosa to carcinogens (e.g. nitrosamines). HIV, common in Malawi, may interfere with H. pylori antibody tests. Limited data, especially from African populations, leaves a gap in understanding the roles of H. pylori and gastric atrophy in ESCC. Methods: We enrolled 300 ESCC cases and 300 controls, matched by age, sex and region, at two Lilongwe, Malawi hospitals (2017-2020) and collected demographic, health, and behavioral data. We measured H. pylori antibodies and gastric atrophy (pepsinogen I (PGI), pepsinogen II (PGII)) via serology. Atrophy was defined as PGI:II <3 or PGI <30μg/L per kit specifications. We adjusted logistic regression models for design variables, known and potential confounders. Results: H. pylori seropositivity was 68% in cases, 80% in controls and significantly associated with lower ESCC risk (aOR 0.54; 95% CI 0.32-0.92). High HIV positivity in cases (21%) may obscure the association due to assay interference. Having a PGI <30μg/L was significantly associated with higher ESCC risk (aOR 4.92; 95% CI 2.04-11.87) while having a PGI:II <3 was marginally associated (aOR 2.14; 95% CI 0.97-4.70). Conclusion: Serologic gastric atrophy was associated with strongly increased ESCC risk. H. pylori's protective effect may be due to measurement interference. Citation Format: Kadiatou Traore, Yingxi Chen, Yukiko Yano, Paul S. Albert, Sung Duk Kim, Sanford M. Dawsey, Shiraz Khan, Christian C. Abnet. Gastric atrophy is associated with increased risk of esophageal squamous cell carcinoma in Lilongwe, Malawi [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6221.