Cadmium exposure and risk of breast cancer: a dose-response meta-analysis of cohort studies

Background: Cadmium is a toxic heavy metal that has been implicated in breast cancer etiology, albeit with inconsistent results. The general population is exposed to cadmium through dietary intake, cigarette smoking, emissions of motorized traffic and industrial facilities. We carried out a systematic review and dose-response meta-analysis of the cohort studies investigating the association between cadmium exposure and breast cancer risk. Methods: Following a literature search through September 10, 2019, we carried out a systematic review and a dose-response meta-analysis to investigate the relation between cadmium exposure and disease risk. We used a restricted cubic spline model and the ‘one-stage’ approach, stratifying for exposure assessment method and menopausal status. Results: We identified eleven studies on breast cancer risk, six based on cadmium dietary intake, and five on urinary excretion levels. In dose-response analysis, we observed a positive, statistically imprecise linear relation between dietary cadmium intake and disease risk. The risk ratio at 20 µg/day compared with no intake was 1.12 (95% confidence interval 0.80-1.56). Conversely, we detected a very imprecise negative association between urinary cadmium excretion and risk (risk ratio=0.89, 95% confidence interval 0.37-2.14 at 2 µg/g creatinine of cadmium excretion). Analysis restricted to post-menopausal women showed substantially no association, as was true for all meta-analyses carried out by comparing the highest versus the lowest exposure category. Conclusions: Overall, we found scant evidence of positive association between cadmium and breast cancer. Available data were too limited to carry out stratified analyses according to age, smoking and hormone receptor status. Therefore, possible associations between cadmium exposure and breast cancer risk in selected subgroups cannot be entirely ruled out. Keywords: cadmium, breast cancer, dietary intake, urine excretion, dose-response meta-analysis