Associations between dietary exposure to profiles of metalloestrogens and estrogen-receptor positive breast cancer risk in the French E3N cohort

Abstract

Metalloestrogens are ionic metals and metalloids that can activate estrogen receptor, and are suspected to play a role in breast cancer occurrence. This study explored the relationship between dietary exposure profiles to metalloestrogens and estrogen-receptor positive breast cancer (ERP-BC) risk among women in the French E3N cohort.A prospective study was conducted involving 66 722 women who completed a food frequency questionnaire in 1993. Food consumption data were combined with food contamination data obtained from the Second French Total Diet Study, to estimate the dietary intake of 14 metalloestrogens. A principal component analysis was performed to identify the main dietary exposure profiles to metalloestrogens. The retained principal components were included in Cox regression models, used to estimate Hazard Ratios (HR) and their 95% confidence intervals (95% CI) for the associations between the adherence to the identified profiles and ERP-BC risk identified until 2014, adjusted for confounding factors selected using a directed acyclic graph.After an average follow-up of 17.7 years, 3 739 incident cases of ERP-BC were identified. Four principal components were retained, explaining 80.5% of the variance. A statistically significant positive association between the third principal component, mainly characterized by dietary intake of inorganic arsenic and vanadium, and ERP-BC risk was estimated (HR: 1.04, 95% CI: 1.00-1.07, p-value: 0.03). No statistically significant association was found when evaluating the effect of each metalloestrogen individually.The results suggests that even relatively low levels of exposure to inorganic arsenic and vanadium, when combined, could increase the risk of ERP-BC.

Keywords: Breast cancer; Dietary exposure to contaminants; Food frequency questionnaire; Metalloestrogens; Principal component analysis; Prospective cohort.