A pooled analysis of dietary sugar/carbohydrate intake and esophageal and gastric cardia adenocarcinoma incidence and survival in the USA

Background: During the past 40 years, esophageal/gastric cardia adenocarcinoma (EA/ GCA) incidence increased in Westernized countries, but survival remained low. A parallel increase in sugar intake, which may facilitate carcinogenesis by promoting hyperglycaemia, led us to examine sugar/carbohydrate intake in association with EA/GCA incidence and survival. Methods: We pooled 500 EA cases, 529 GCA cases and 2027 controls from two US population-based case-control studies with cases followed for vital status. Dietary intake, assessed by study-specific food frequency questionnaires, was harmonized and pooled to estimate 12 measures of sugar/carbohydrate intake. Multivariable-adjusted odds ratios (ORs) and hazard ratios [95% confidence intervals (CIs)] were calculated using multinomial logistic regression and Cox proportional hazards regression, respectively. Results: EA incidence was increased by 51-58% in association with sucrose (ORQ5vs.Q1=1.51, 95% CI=1.01-2.27), sweetened desserts/beverages (ORQ5vs.Q1=1.55, 95% CI=1.06-2.27) and the dietary glycaemic index (ORQ5vs.Q1=1.58, 95% CI=1.13-2.21). Bodymass index (BMI) and gastro-esophageal reflux disease (GERD) modified these associations (Pmultiplicative-interaction ≤ 0.05). For associations with sucrose and sweetened desserts/beverages, respectively, the OR was elevated for BMI < 25 (ORQ4-5vs.Q1-3=1.79, 95% CI=1.26-2.56 and ORQ4-5vs.Q1-3=1.45, 95% CI=1.03-2.06), but not BMI≥25 (ORQ4-5vs.Q1-3=1.05, 95% CI=0.76-1.44 and ORQ4-5vs.Q1-3=0.85, 95% CI=0.62-1.16). The EA-glycaemic index association was elevated for BMI≥25 (ORQ4-5vs.Q1-3=1.38, 95% CI=1.03-1.85), but not BMI < 25 (ORQ4-5vs.Q1-3=0.88, 95% CI=0.62-1.24). The sucrose-EA association OR for GERD < weekly was 1.58 (95% CI=1.16-2.14), but for GERD≥weekly was 1.01 (95% CI=0.70-1.47). Sugar/carbohydrate measures were not associated with GCA incidence or EA/GCA survival. Conclusions: If confirmed, limiting intake of sucrose (e.g. table sugar), sweetened desserts/ beverages, and foods that contribute to a high glycaemic index, may be plausible EA risk reduction strategies