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

Background and aim: Cadmium is a heavy metal which has been implicated in breast cancer etiology because of its toxic properties such as endocrine disruption. 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, for which inconsistent results have been reported in the literature. Methods: Following online database search up to January 2019, we carried out a dose-response meta-analysis to identify the relation between cadmium exposure and disease risk. We used a restricted cubic spline model and the \u2018one-stage\u2019 approach, stratifying for exposure assessment method and menopausal status. Results: We identified 12 studies, 9 using breast cancer incidence and 3 mortality as an outcome. In six studies cadmium exposure was assessed through dietary questionnaires, in five through urinary excretion levels, and in one based on environmental air levels. Seven studies included post-menopausal women only. Overall, we observed a positive linear relation between breast cancer risk and dietary cadmium intake (relative risk (RR) 1.04, 95% confidence interval (CI) 0.81-1.33 at 10 \ub5g/day, and RR 1.12, 95% CI 0.80-1.56 at 20 \ub5g/day). On the converse, risk was not associated with urinary excretion. Analysis restricted to post-menopausal women showed a positive association between cadmium exposure assessed through either dietary intake and urinary excretion, for levels higher than 20 \ub5g/day and 1.65 \ub5g/g creatinine, respectively

Potassium Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials

BACKGROUND: Epidemiologic studies, including trials, suggest an association between potassium intake and blood pressure (BP). However, the strength and shape of this relationship is uncertain. METHODS AND RESULTS: We performed a meta-analysis to explore the dose-response relationship between potassium supplementation and BP in randomized-controlled trials with a duration >= 4 weeks using the recently developed 1-stage cubic spline regression model. This model allows use of trials with at least 2 exposure categories. We identified 32 eligible trials. Most were conducted in adults with hypertension using a crossover design and potassium supplementation doses that ranged from 30 to 140 mmol/d. We observed a U-shaped relationship between 24-hour active and control arm differences in potassium excretion and BP levels, with weakening of the BP reduction effect above differences of 30 mmol/d and a BP increase above differences similar to 80 mmol/d. Achieved potassium excretion analysis also identified a U-shaped relationship. The BP-lowering effects of potassium supplementation were stronger in participants with hypertension and at higher levels of sodium intake. The BP increase with high potassium excretion was noted in participants with antihypertensive drug-treated hypertension but not in their untreated counterparts. CONCLUSIONS: We identified a nonlinear relationship between potassium intake and both systolic and diastolic BP, although estimates for BP effects of high potassium intakes should be interpreted with caution because of limited availability of trials. Our findings indicate an adequate intake of potassium is desirable to achieve a lower BP level but suggest excessive potassium supplementation should be avoided, particularly in specific subgroups

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. Objective. To investigate the shape of the relation between cadmium exposure and breast cancer incidence and mortality in cohort studies. Data sources. Following a literature search through April 14, 2020, we carried out a systematic review and dose-response meta-analysis to investigate the shape of the relation between cadmium exposure (assessed either through diet or urine excretion) and disease incidence and mortality. Study eligibility criteria. For inclusion, a study had to report incidence or mortality for breast cancer according to baseline cadmium exposure category; be a prospective cohort, case-cohort or nested case-control study with a minimum one-year follow-up, and reporting effect estimates for all exposure categories. Study appraisal and synthesis methods. Studies were evaluated using the ROBINS-E risk of bias tool. The effects in humans were assessed quantitatively using one-stage dose-response meta-analysis in a random effects meta-analytical model. Results. We identified 10 studies eligible for inclusion in the dose-response meta-analysis, six based on cadmium dietary intake, and four on urinary excretion levels. We found a marginal and imprecise positive relation between dietary cadmium intake and breast cancer, and no association when urinary cadmium excretion was used for exposure assessment. Compared to no exposure, at 20 µg/day of cadmium intake the summary risk ratio was 1.12 (95% confidence interval 0.80–1.56), while at 2 µg/g creatinine of cadmium excretion the summary risk ratio was 0.89 (95% confidence interval 0.38–2.14). Analysis restricted to post-menopausal women showed no association between either dietary or urinary cadmium and subsequent breast cancer incidence and mortality. Limitations and conclusions. Overall, we found scant evidence of a 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 in selected subgroups cannot be entirely ruled out.Supported by grant GP-EFSA-AFSCO-2017-01 GA09 of the European Food Safety Authority - EFSA