Serum heavy metals and breast cancer risk: A case-control study nested in the Florence cohort of the EPIC (European Prospective Investigation into Cancer and nutrition) study

Chronic exposure to heavy metals is of concern for its potential carcinogenic effect. An association with increased breast cancer (BC) risk was hypothesized, but literature data are conflicting and the question remains unresolved. We aimed to investigate the association between heavy metals and BC risk in a case-control study nested within the Florence section of the EPIC (European Prospective Investigation into Cancer and nutrition) cohort.We included 150 BC cases and an equal number of controls individually matched to cases by age and year of enrolment. In order to avoid confounding by smoking, the study was restricted to never smokers. Serum levels of six heavy metals (Cd, Co, Cr, Mn, Pb, and Tl) were quantified in pre-diagnostic samples using inductively coupled plasma mass spectrometry. Odds ratios (ORs) and corresponding 95 % confidence intervals (CI) were calculated via multivariable conditional logistic regression models.Serum levels of cobalt were inversely associated with BC risk (OR for the comparison of 3rd vs. 1st tertiles: 0.33, 95 % CI 0.12-0.91, p-value 0.033). None of the other heavy metals under study was significantly associated with BC risk in multivariable models. For Cd, Cr, and Tl, over half of the study participants had serum levels below the limit of quantitation.Our results do not support the hypothesis that exposure to heavy metals is associated with an increased BC risk among never smokers from the general population. The inverse association between cobalt serum levels and BC risk requires confirmation in future studies.