Selenium Status and the Risk of Esophageal and Gastric Cancer Subtypes: The Netherlands Cohort Study

BACKGROUND & AIMS: Selenium may protect against the development of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), and gastric cardia adenocarcinoma (GCA). Only in very few studies have the associations with ESCC and GCA been investigated, and no epidemiologic studies exist on EAC. METHODS: We studied the association between selenium and risk of ESCC, EAC, and GCA within the prospective Netherlands Cohort Study, conducted among 120,852 men and women aged 55-69 years at baseline. In September 1986, the cohort members completed a questionnaire on risk factors for cancer and provided toenail clippings for determination of baseline selenium status. After 16.3 years of follow-up, 64 ESCC, 112 EAC, and 114 GCA cases and 2072 subcohort members were available for case-cohort analysis. Incidence rate ratios (RR) were calculated using Cox proportional hazards models. RESULTS: In multivariable analyses of selenium status, we found an inverse association with ESCC (RRper standard unit increment, 0.80; 95% confidence interval [CI]: 0.67-0.96) and a borderline significant inverse association with GCA (RR, 0.91; 95% CI: 0.80-1.02). No overall association was observed for EAC (RR, 1.05; 95% CI: 0.95-1.15), but, for women and never smokers, significant inverse associations were found (0.72; 95% CI: 0.61-0.84 RRper standard umt Increment) and RRper standard unit Increment) 0.74; 95% CI: 0.64-0.86, respectively). CONCLUSIONS: This prospective study supports an inverse association between toenail selenium and risk of ESCC and GCA and suggests an inverse association with risk of EAC in subgroups (women, never smokers, and low antioxidant consumers). These associations need confirmation