Dietary N-nitroso compounds, endogenous nitrosation, and the risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study1–3

Background: Dietary N-nitroso compounds and endogenous nitro-sation are important carcinogenic factors, but human evidence of their role is scarce for esophageal cancer and inconsistent for gastric cancer. Objective: We studied the relation between risks of esophageal and gastric cancer subtypes and dietary intake of N-nitrosodimethylamine, heme iron, nitrite, and nitrate in the Netherlands Cohort Study. Design: A total of 120,852 men and women aged 55–69 y were recruited in 1986, and diet, based on a 150-item food-frequency questionnaire, and other risk factors were assessed. The cohort was followed for 16.3 y, and 110 esophageal squamous cell carcinoma (ESCC), 151 esophageal adenocarcinoma, 166 gastric cardia adeno-carcinoma, and 497 gastric noncardia adenocarcinoma (GNCA) cases were analyzed along with 4032 subcohort members in a case-cohort analysis. Results: Positive associations were observed between N-nitrosodi-methylamine intake and ESCC risk (HR for 0.1-mg/d increase in intake: 1.15; 95 % CI: 1.05, 1.25; P-trend = 0.01 based on tertiles o