Lifestyle and Environmental Risk Factors for Esophageal Squamous Cell Carcinoma: Evidence From the Johannesburg Cancer Study

PURPOSE: Esophageal squamous cell carcinoma (ESCC) remains a major cause of cancer mortality in South Africa. Understanding locally relevant and modifiable risk factors is crucial for prevention. This study clarifies the syndemic role of lifestyle and environmental factors, such as alcohol, tobacco, socioeconomic indicators (rurality and education), and fuel use, in ESCC. METHODS: We analyzed 939 histologically confirmed ESCC cases and 3,089 cancer controls from the Johannesburg Cancer Study. Multivariable logistic regression estimated adjusted odds ratios (aORs), with interaction terms for alcohol, tobacco, and sex. Population attributable fractions were calculated using both study-control and national prevalence estimates. RESULTS: Very high alcohol intake (≥840 g ethanol/wk) showed a modest independent association with ESCC (aOR, 1.56 [95% CI, 1.14 to 2.12]). Smoking was a strong risk factor, with aOR = 2.82 (95% CI, 2.20 to 3.62) for ex-smokers and 6.71 (95% CI, 5.15 to 8.76) for current smokers. Among never-smokers, alcohol showed little dose response. Among smokers, risks were high across all alcohol levels, with no consistent increase at higher intakes. Additional risks included rural origin or residence (aOR approximately equal to 1.22-2.38), lower educational attainment (aOR approximately equal to 1.45-1.69), and use of biomass or other fuels (aOR, 1.50 [95% CI, 1.21 to 1.87]). CONCLUSION: In this high-burden setting, tobacco remains the principal modifiable driver of ESCC. Alcohol showed only a modest independent effect, limited to very high intake, and did not increase the risk among smokers beyond the high risk from smoking. Socioeconomic and environmental disadvantages cluster with behavioral risks, underscoring a syndemic context. These findings, consistent with prior Johannesburg Cancer Study reports yet offering greater exposure granularity, support targeted prevention strategies focused on smoking cessation, mitigation of hazardous drinking patterns, and reduction of household environmental exposures.