Gluten Intake and Risk of Digestive System Cancers in 3 Large Prospective Cohort Studies

Background & Aims: In patients with celiac disease, gluten triggers an immune reaction that damages small intestinal villi and may increase long-term risk of gastrointestinal cancer. However, the health impacts of gluten in the general population are understudied. We aimed to examine the association between gluten intake and risk of digestive system cancers among individuals without celiac disease. Methods: We leveraged longitudinal data from 3 prospective cohorts, the Nurses’ Health Study (1984–2018, 73,166 women aged 65.1 ± 10.8 years), Nurses’ Health Study II (1991–2017, 90,423 women aged 49.1 ± 8.2 years), and Health Professionals Follow-Up Study (1986–2016, 42,617 men aged 64.8 ± 10.8 years). Using Cox proportional hazards regression, we estimated hazard ratios and 95% confidence intervals of digestive system cancers according to quintiles of gluten intake assessed from food frequency questionnaires. Results: During 4,801,513 person-years of follow-up, we documented 6231 incident digestive system cancer cases among 3 cohorts. After adjusting for a wide-range of risk factors, including body mass index, physical activity, diet quality, gluten intake was not associated with an increased risk of digestive system cancer, with a hazard ratio of 0.94 (95% confidence interval, 0.87–1.02) comparing the highest with the lowest quintile of gluten intake (P trend = .05). Similar null associations were found for individual digestive system cancers: oral cavity and oropharyngeal cancer, esophageal cancer, stomach cancer, small intestine cancer, colorectal cancer, pancreatic cancer, gallbladder cancer, and liver cancer. Conclusions: Gluten intake was not associated with risk of digestive system cancers in adults without celiac disease. Restricting dietary gluten is unlikely to be beneficial to the prevention of digestive system cancers in the general population.