title: Dietary exposure to cadmium and risk of breast cancer in postmenopausal women: A systematic review and meta-analysis.
abstract: BACKGROUND
  With tobacco smoking, diet is the main source of cadmium (Cd) exposure in the general population. The carcinogenic and estrogenic activities of Cd make it a contaminant of potential concern for hormone-dependent cancers including breast cancer. Postmenopausal women represent the most appropriate population to investigate the possible impact of exogenous factors with potential estrogenic activity on breast cancer as, after menopause, their estrogenic influence is predominant.
  
  
  OBJECTIVE
  We systematically reviewed available studies on the association between dietary exposure to Cd and breast cancer focusing on postmenopausal women. A meta-analysis combining the risk estimators was performed and potential sources of between studies heterogeneity were traced.
  
  
  METHODS
  Studies were searched from MEDLINE through 31 January 2015 and from the reference lists of relevant publications. Six eligible studies published between 2012 and 2014 were identified and relative risk estimates were extracted. Meta-rate ratio estimates (mRR) were calculated according to fixed and random-effect models. Meta-analyses were performed on the whole set of data and separate analyses were conducted after stratification for study design, geographic location, use of hormone replacement therapy (HRT), tumor estrogen receptor status (ER+ or ER-), progesterone receptor status (PGR+ or PGR-), body mass index (BMI), smoker status, zinc or iron intake.
  
  
  RESULTS
  No statistically significant increased risk of breast cancer was observed when all studies were combined (mRR=1.03; 95% confidence interval [CI]: 0.89-1.19). Several sources of heterogeneity and inconsistency were identified, including smoker status, HRT use, BMI, zinc and iron intake. Inconsistency was also strongly reduced when only considering ER-, PGR-, tumors subgroups from USA and from Japan. The risks were, however, not substantially modified after stratifications. No evidence of publication bias was found.
  
  
  CONCLUSIONS
  The present study does not provide support for the hypothesis that dietary exposure to Cd increases the risk of breast cancer in postmenopausal women. Misclassification in dietary Cd assessment in primary studies could have biased the results towards a finding of no association.
authors.affiliation: Université catholique de Louvain, SSS/IREC/LTAP (Louvain Center for Toxicology and Applied Pharmacology), Avenue E. Mounier 53, bte B1.52.12, B-1200 Brussels, Belgium. Electronic address: genevieve.vanmaele@uclouvain.be.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Van Maele-Fabry
authors.affiliation: International Zinc/Cadmium Association, Avenue de Tervueren 168/Box 4, B-1150 Brussels, Belgium. Electronic address: nlombaert@zinc.org.
authors.forename: Noömi
authors.initials: N
authors.lastname: Lombaert
authors.affiliation: Université catholique de Louvain, SSS/IREC/LTAP (Louvain Center for Toxicology and Applied Pharmacology), Avenue E. Mounier 53, bte B1.52.12, B-1200 Brussels, Belgium. Electronic address: dominique.lison@uclouvain.be.
authors.forename: Dominique
authors.initials: D
authors.lastname: Lison
mesh_terms: D000328:Adult; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000453:epidemiology*; D002104:Cadmium / Q000032:analysis* / Q000493:pharmacokinetics; D004032:Diet; D004781:Environmental Exposure / Q000032:analysis* / Q000706:statistics & numerical data; D004785:Environmental Pollutants / Q000032:analysis* / Q000493:pharmacokinetics; D005247:Feeding Behavior; D005260:Female; D005506:Food Contamination / Q000032:analysis*; D006801:Humans; D007564:Japan; D008875:Middle Aged; D017698:Postmenopause / Q000378:metabolism*; D018570:Risk Assessment
chemical_list: D004785:Environmental Pollutants; D002104:Cadmium
keywords: Breast cancer; Dietary cadmium; Meta-analysis; Postmenopausal women; Systematic review