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.

中文翻译：

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镉暴露与乳腺癌风险：队列研究的剂量反应荟萃分析。

背景

镉是一种有毒的重金属，尽管结果不一致，但已与乳腺癌的病因有关。

目的

在队列研究中调查镉暴露与乳腺癌发病率和死亡率之间关系的形状。

数据源

经过2020年4月14日的文献检索，我们进行了系统的综述和剂量反应荟萃分析，研究了镉暴露（通过饮食或尿液排泄评估）与疾病发病率和死亡率之间的关系。

研究资格标准

为了纳入研究，必须根据基线镉暴露类别报告乳腺癌的发病率或死亡率。是一项前瞻性队列研究，病例队列研究或嵌套病例对照研究，至少要进行一年的随访，并报告所有暴露类别的效果评估。

学习评估和综合方法

使用ROBINS-E偏倚风险工具评估研究。使用随机效应荟萃分析模型中的一阶段剂量反应荟萃分析对人类的效应进行了定量评估。

结果

我们确定了10项适合纳入剂量反应荟萃分析的研究，其中6项基于镉的饮食摄入量，另外4项基于尿排泄水平。我们发现饮食中镉摄入量与乳腺癌之间的边际和不精确的正相关关系，而当尿镉排泄量用于暴露评估时则没有关联。与不暴露相比，每天摄入20 µg镉时，汇总风险比为1.12（95％置信区间0.80–1.56），而当摄入2 µg / g肌酐时，镉汇总风险比为0.89（95％置信区间） 0.38–2.14）。仅限绝经后妇女的分析表明，饮食中或尿中的镉与随后的乳腺癌发病率和死亡率之间没有关联。

局限性和结论

总体而言，我们几乎没有发现镉与乳腺癌之间存在正相关的证据。现有数据太有限，无法根据年龄，吸烟和激素受体状态进行分层分析。因此，不能完全排除某些亚组中镉暴露与乳腺癌之间的可能联系。