Iron intake, body iron status, and risk of breast cancer: a systematic review and meta-analysis

Abstract Background Iron has been shown to promote breast carcinogenesis in animal models through generation of oxidative stress and interaction with estrogen. Heme iron, which is found exclusively in animal-sourced foods, is suggested to have a more detrimental effect. Epidemiological evidence of t...

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Main Authors: Vicky C. Chang, Michelle Cotterchio, Edwin Khoo
Format: Article
Language:English
Published: BMC 2019-06-01
Series:BMC Cancer
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12885-019-5642-0
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author Vicky C. Chang
Michelle Cotterchio
Edwin Khoo
author_facet Vicky C. Chang
Michelle Cotterchio
Edwin Khoo
author_sort Vicky C. Chang
collection DOAJ
description Abstract Background Iron has been shown to promote breast carcinogenesis in animal models through generation of oxidative stress and interaction with estrogen. Heme iron, which is found exclusively in animal-sourced foods, is suggested to have a more detrimental effect. Epidemiological evidence of the association between iron and breast cancer risk remains inconclusive and has not been comprehensively summarized. This systematic review and meta-analysis evaluated associations between both iron intake and body iron status and breast cancer risk. Methods Four electronic databases (MEDLINE, EMBASE, CINAHL, and Scopus) were searched up to December 2018 for studies assessing iron intake and/or biomarkers of iron status in relation to breast cancer risk. Using random-effects meta-analyses, pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated comparing the highest vs. lowest category of each iron measure. Dose-response meta-analyses were also performed to investigate linear and nonlinear associations. Results A total of 27 studies were included in the review, of which 23 were eligible for meta-analysis of one or more iron intake/status measures. Comparing the highest vs. lowest category, heme iron intake was significantly associated with increased breast cancer risk, with a pooled RR of 1.12 (95% CI: 1.04–1.22), whereas no associations were found for dietary (1.01, 95% CI: 0.89–1.15), supplemental (1.02, 95% CI: 0.91–1.13), or total (0.97, 95% CI: 0.82–1.14) iron intake. Associations of iron status indicators with breast cancer risk were generally in the positive direction; however, a significant pooled RR was found only for serum/plasma levels (highest vs. lowest) of iron (1.22, 95% CI: 1.01–1.47), but not for ferritin (1.13, 95% CI: 0.78–1.62), transferrin saturation (1.16, 95% CI: 0.91–1.47), or total iron-binding capacity (1.10, 95% CI: 0.97–1.25). In addition, a nonlinear dose-response was observed for heme iron intake and serum iron (both P nonlinearity < 0.05). Conclusions Heme iron intake and serum iron levels may be positively associated with breast cancer risk. Although associations were modest, these findings may have public health implications given the widespread consumption of (heme) iron-rich foods. In light of methodological and research gaps identified, further research is warranted to better elucidate the relationship between iron and breast cancer risk.
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spelling doaj.art-b0b9b7e4ebd5471e87e5667c90243ed12022-12-21T18:57:16ZengBMCBMC Cancer1471-24072019-06-0119112810.1186/s12885-019-5642-0Iron intake, body iron status, and risk of breast cancer: a systematic review and meta-analysisVicky C. Chang0Michelle Cotterchio1Edwin Khoo2Dalla Lana School of Public Health, University of TorontoDalla Lana School of Public Health, University of TorontoAnalytics and Informatics, Cancer Care OntarioAbstract Background Iron has been shown to promote breast carcinogenesis in animal models through generation of oxidative stress and interaction with estrogen. Heme iron, which is found exclusively in animal-sourced foods, is suggested to have a more detrimental effect. Epidemiological evidence of the association between iron and breast cancer risk remains inconclusive and has not been comprehensively summarized. This systematic review and meta-analysis evaluated associations between both iron intake and body iron status and breast cancer risk. Methods Four electronic databases (MEDLINE, EMBASE, CINAHL, and Scopus) were searched up to December 2018 for studies assessing iron intake and/or biomarkers of iron status in relation to breast cancer risk. Using random-effects meta-analyses, pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated comparing the highest vs. lowest category of each iron measure. Dose-response meta-analyses were also performed to investigate linear and nonlinear associations. Results A total of 27 studies were included in the review, of which 23 were eligible for meta-analysis of one or more iron intake/status measures. Comparing the highest vs. lowest category, heme iron intake was significantly associated with increased breast cancer risk, with a pooled RR of 1.12 (95% CI: 1.04–1.22), whereas no associations were found for dietary (1.01, 95% CI: 0.89–1.15), supplemental (1.02, 95% CI: 0.91–1.13), or total (0.97, 95% CI: 0.82–1.14) iron intake. Associations of iron status indicators with breast cancer risk were generally in the positive direction; however, a significant pooled RR was found only for serum/plasma levels (highest vs. lowest) of iron (1.22, 95% CI: 1.01–1.47), but not for ferritin (1.13, 95% CI: 0.78–1.62), transferrin saturation (1.16, 95% CI: 0.91–1.47), or total iron-binding capacity (1.10, 95% CI: 0.97–1.25). In addition, a nonlinear dose-response was observed for heme iron intake and serum iron (both P nonlinearity < 0.05). Conclusions Heme iron intake and serum iron levels may be positively associated with breast cancer risk. Although associations were modest, these findings may have public health implications given the widespread consumption of (heme) iron-rich foods. In light of methodological and research gaps identified, further research is warranted to better elucidate the relationship between iron and breast cancer risk.http://link.springer.com/article/10.1186/s12885-019-5642-0Breast cancerIron intakeHeme ironIron statusFerritinSystematic review
spellingShingle Vicky C. Chang
Michelle Cotterchio
Edwin Khoo
Iron intake, body iron status, and risk of breast cancer: a systematic review and meta-analysis
BMC Cancer
Breast cancer
Iron intake
Heme iron
Iron status
Ferritin
Systematic review
title Iron intake, body iron status, and risk of breast cancer: a systematic review and meta-analysis
title_full Iron intake, body iron status, and risk of breast cancer: a systematic review and meta-analysis
title_fullStr Iron intake, body iron status, and risk of breast cancer: a systematic review and meta-analysis
title_full_unstemmed Iron intake, body iron status, and risk of breast cancer: a systematic review and meta-analysis
title_short Iron intake, body iron status, and risk of breast cancer: a systematic review and meta-analysis
title_sort iron intake body iron status and risk of breast cancer a systematic review and meta analysis
topic Breast cancer
Iron intake
Heme iron
Iron status
Ferritin
Systematic review
url http://link.springer.com/article/10.1186/s12885-019-5642-0
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