{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:27:00Z","timestamp":1787498820692,"version":"build-2736575974"},"reference-count":68,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,10,28]],"date-time":"2020-10-28T00:00:00Z","timestamp":1603843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Arsenic is a widespread environmental contaminant and recognized carcinogen for the skin, bladder and lungs. In recent years, there has been an increasing number of studies that have investigated the effects of arsenic exposure and cancer risk at other sites, including the breast. However, to date, the association between arsenic exposure and breast cancer risk remains unclear. This article will provide an overview of arsenic metabolism, the clinically important biomarkers commonly used to assess arsenic exposure, and review the epidemiologic studies examining the role of arsenic exposure on breast cancer risk. Given the large burden of disease associated with breast cancer, it is of the upmost importance to identify risk factors and preventative strategies that could reduce cancer incidence. Limiting exposure to endemic environmental toxins, such as arsenic, represents one such strategy. More studies are required to better ascertain this relationship and to develop the public policy necessary to significantly reduce breast cancer incidence.<\/jats:p>","DOI":"10.3390\/nu12113305","type":"journal-article","created":{"date-parts":[[2020,10,28]],"date-time":"2020-10-28T11:43:06Z","timestamp":1603885386000},"page":"3305","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Arsenic Exposure and Breast Cancer Risk: A Re-Evaluation of the Literature"],"prefix":"10.3390","volume":"12","author":[{"given":"Katherine","family":"Pullella","sequence":"first","affiliation":[{"name":"Department of Nutritional Sciences, University of Toronto, Toronto, ON M5S 1A1, Canada"},{"name":"Women\u2019s College Research Institute, Women\u2019s College Hospital, Toronto, ON M5S 1B2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Kotsopoulos","sequence":"additional","affiliation":[{"name":"Women\u2019s College Research Institute, Women\u2019s College Hospital, Toronto, ON M5S 1B2, Canada"},{"name":"Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5T 3M7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,28]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2018, September 20). Arsenic. Available online: http:\/\/www.who.int\/news-room\/fact-sheets\/detail\/arsenic."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1136\/pmj.79.933.391","article-title":"Acute and chronic arsenic toxicity","volume":"79","author":"Ratnaike","year":"2003","journal-title":"Postgrad. Med. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1289\/ehp.814093","article-title":"The carcinogenicity of arsenic","volume":"40","author":"Pershagen","year":"1981","journal-title":"Environ. Health Perspect."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"253","DOI":"10.3961\/jpmph.14.036","article-title":"Environmental source of arsenic exposure","volume":"47","author":"Chung","year":"2014","journal-title":"J. Prev. Med. Public Health"},{"key":"ref_5","unstructured":"International Agency for Research on Cancer (IARC) (2012). Arsenic Metals, Fibres and Dusts: A review of human carcinogens, International Agency for Research on Cancer."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1289\/ehp.1205875","article-title":"The broad scope of health effects from chronic arsenic exposure: Update on a worldwide public health problem","volume":"121","author":"Naujokas","year":"2013","journal-title":"Environ. Health Perspect."},{"key":"ref_7","unstructured":"Agency for Toxic Substances and Disease Registry (2007). Toxicological Profile for Arsenic."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s40726-019-0102-7","article-title":"Arsenic in Drinking Water: Is 10 \u03bcg\/L a Safe Limit?","volume":"5","author":"Ahmad","year":"2019","journal-title":"Curr. Pollut. Rep."},{"key":"ref_9","unstructured":"World Health Organization (2008). Guidelines for Drinking-Water Quality, World Health Organization. [3rd ed.]."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1093\/toxsci\/kfr184","article-title":"Arsenic exposure and toxicology: A historical perspective","volume":"123","author":"Hughes","year":"2011","journal-title":"Toxicol. Sci."},{"key":"ref_11","unstructured":"Kuivenhoven, M., and Mason, K. (2019). Arsenic (Arsine) Toxicity. StatPearls, StatPearls Publishing LLC."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.jtemb.2015.01.010","article-title":"Arsenic in the human food chain, biotransformation and toxicology--Review focusing on seafood arsenic","volume":"31","author":"Molin","year":"2015","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1021\/acs.jafc.9b07532","article-title":"Organoarsenicals in Seafood: Occurrence, Dietary Exposure, Toxicity, and Risk Assessment Considerations\u2014A Review","volume":"68","author":"Luvonga","year":"2020","journal-title":"J. Agric. Food Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.envres.2017.08.045","article-title":"Environmental chemicals and breast cancer: An updated review of epidemiological literature informed by biological mechanisms","volume":"160","author":"Rodgers","year":"2018","journal-title":"Environ. Res."},{"key":"ref_15","unstructured":"World Cancer Research Fund (2018). Continuous Update Project Expert Report 2018. Diet, Nutrition, Physical Activity and Breast Cancer, American Institute for Cancer Research."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/0471140856.tx0431s42","article-title":"An Overview of Arsenic Metabolism and Toxicity","volume":"42","author":"Drobna","year":"2009","journal-title":"Curr. Protoc. Toxicol."},{"key":"ref_17","first-page":"429","article-title":"Biological methylation","volume":"12","author":"Challenger","year":"1951","journal-title":"Adv. Enzymol. Relat. Subj. Biochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1146\/annurev-nutr-082117-051757","article-title":"Nutritional Influences on One-Carbon Metabolism: Effects on Arsenic Methylation and Toxicity","volume":"38","author":"Bozack","year":"2018","journal-title":"Annu. Rev. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"108700","DOI":"10.1016\/j.envres.2019.108700","article-title":"Biological and molecular modifications induced by cadmium and arsenic during breast and prostate cancer development","volume":"178","author":"Zimta","year":"2019","journal-title":"Environ. Res."},{"key":"ref_20","unstructured":"National Centre for Biotechnology Information (2020, August 03). PubChem Compound Summary for CID 8948, Methylarsonic acid, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Methylarsonic-acid."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1002\/bdrb.20065","article-title":"Monomethylarsonic acid and dimethylarsinic acid: Developmental toxicity studies with risk assessment","volume":"77","author":"Irvine","year":"2006","journal-title":"Birth Defects Res. B. Dev. Reprod. Toxicol."},{"key":"ref_22","first-page":"157","article-title":"Glutathione Reductase Inhibition and Methylated Arsenic Distribution in Cd1 Mice Brain and Liver","volume":"84","author":"Giordano","year":"2004","journal-title":"Toxic. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s00204-004-0620-x","article-title":"A new metabolic pathway of arsenite: Arsenic-glutathione complexes are substrates for human arsenic methyltransferase Cyt19","volume":"79","author":"Hayakawa","year":"2005","journal-title":"Arch. Toxicol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s10552-006-0057-z","article-title":"Trace elements and cancer risk: A review of the epidemiologic evidence","volume":"18","author":"Rohan","year":"2007","journal-title":"Cancer Causes Control."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1002\/mnfr.201501063","article-title":"Epigenetics of breast cancer: Modifying role of environmental and bioactive food compounds","volume":"60","author":"Romagnolo","year":"2016","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.envres.2017.04.016","article-title":"Arsenic metabolism and cancer risk: A meta-analysis","volume":"156","author":"Cebrian","year":"2017","journal-title":"Environ. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1289\/ehp.11872","article-title":"Folate deficiency, hyperhomocysteinemia, low urinary creatinine, and hypomethylation of leukocyte DNA are risk factors for arsenic-induced skin lesions","volume":"117","author":"Pilsner","year":"2009","journal-title":"Environ. Health Perspect."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"87","DOI":"10.4103\/0971-6580.84258","article-title":"Mechanisms pertaining to arsenic toxicity","volume":"18","author":"Singh","year":"2011","journal-title":"Toxicol. Int."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Rakib, M., Huda, M., Hossain, S., Naher, K., Khan, R., Sultana, M., Akter, M., Bhuiyan, M., and Patwary, M. (2013). Arsenic Content in Inactive Tissue: Human Hair and Nail. J. Scien. Res. Rep.","DOI":"10.9734\/JSRR\/2013\/3091"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1289\/ehp.9058","article-title":"Biomarkers of exposure: A case study with inorganic arsenic","volume":"114","author":"Hughes","year":"2006","journal-title":"Environ. Health Perspect."},{"key":"ref_31","first-page":"171","article-title":"Markers of low level arsenic exposure for evaluating human cancer risks in a US population","volume":"14","author":"Karagas","year":"2001","journal-title":"Int. J. Occup. Med. Environ. Health"},{"key":"ref_32","first-page":"493","article-title":"Toenail trace element levels as biomarkers: Reproducibility over a 6-year period","volume":"2","author":"Garland","year":"1993","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1080\/10937400903358934","article-title":"Biomonitoring for Environmental Exposures to Arsenic","volume":"12","author":"Orloff","year":"2009","journal-title":"J. Toxic. Environ. Health Part B"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/jes.2013.80","article-title":"Biomarkers of arsenic exposure and effects in a Canadian rural population exposed through groundwater consumption","volume":"24","author":"Normandin","year":"2014","journal-title":"J. Exp. Scien. Environ. Epidem."},{"key":"ref_35","unstructured":"National Research Council (US) (1999). Subcommittee on Arsenic in Drinking Water, Arsenic in Drinking Water, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK230893."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.envint.2011.07.015","article-title":"What is the best biomarker to assess arsenic exposure via drinking water?","volume":"39","author":"Savanovitch","year":"2012","journal-title":"Environ. Int."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.tox.2006.06.010","article-title":"Blood arsenic as a biomarker of arsenic exposure: Results from a prospective study","volume":"225","author":"Hall","year":"2006","journal-title":"Toxicology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1038\/s41370-019-0121-x","article-title":"Evaluation of plasma arsenicals as potential biomarkers of exposure to inorganic arsenic","volume":"29","author":"Bommarito","year":"2019","journal-title":"J. Expo. Sci. Environ. Epidemiol."},{"key":"ref_39","unstructured":"Agency for Toxic Substances and Disease Registry, (ATSDR), and Gehle, K. (2020, January 21). Arsenic Toxicity, Available online: https:\/\/www.atsdr.cdc.gov\/csem\/csem.asp?csem=1&po=0."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.yrtph.2010.06.002","article-title":"Biomonitoring equivalents for inorganic arsenic","volume":"58","author":"Hays","year":"2010","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1289\/ehp.7337","article-title":"Urinary creatinine concentrations in the U.S. population: Implications for urinary biologic monitoring measurements","volume":"113","author":"Barr","year":"2005","journal-title":"Environ. Health Perspect."},{"key":"ref_42","unstructured":"New Zealand Worksafe (2018). Biological Exposures Indicies, PO Box 165."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.amjhyper.2005.04.002","article-title":"Limitations of an Ecological Study: A Review","volume":"18","author":"Cohen","year":"2005","journal-title":"Am. J. Hypertension"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1080\/09603129973272","article-title":"Cancer incidence and high environmental arsenic concentrations in rural populations: Results of an ecological study","volume":"9","author":"Hinwood","year":"1999","journal-title":"Int. J. Environ. Health Research"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1289\/ehp.10623","article-title":"Arsenic in drinking-water and risk for cancer in Denmark","volume":"116","author":"Baastrup","year":"2008","journal-title":"Environ. Health Perspect."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1080\/09513590.2019.1622089","article-title":"Endocrine-disrupting metals in ambient air and female breast cancer incidence in US","volume":"35","author":"Vu","year":"2019","journal-title":"Gynecol. Endocrinol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1080\/09603123.2011.628792","article-title":"Cancer incidence and pattern of arsenic concentration in drinking water wells in Cordoba, Argentina","volume":"22","author":"Aballay","year":"2012","journal-title":"Int. J. Environ. Health Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1038\/sj.bjc.6605637","article-title":"Occupation and cancer in Britain","volume":"102","author":"Rushton","year":"2010","journal-title":"Br. J. Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/BF02789296","article-title":"An elemental correlation study in cancerous and normal breast tissue with successive clinical stages by neutron activation analysis","volume":"46","author":"Garg","year":"1994","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/s12011-008-8281-x","article-title":"Hair iron and other minerals\u2019 level in breast cancer patients","volume":"129","author":"Joo","year":"2009","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1007\/s12011-011-9104-z","article-title":"Trace elements and heavy metals in hair of stage III breast cancer patients","volume":"144","author":"Sozen","year":"2011","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.cca.2014.10.007","article-title":"Naeemullah. Interaction between carcinogenic and anti-carcinogenic trace elements in the scalp hair samples of different types of Pakistani female cancer patients","volume":"439","author":"Wadhwa","year":"2015","journal-title":"Clin. Chim. Acta."},{"key":"ref_53","first-page":"1","article-title":"Comparing the metal concentration in the hair of cancer patients and healthy people living in the malwa region of punjab, India","volume":"8","author":"Busch","year":"2014","journal-title":"Clin. Med. Insights Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s12011-010-8608-2","article-title":"Lead exposure: A contributing cause of the current breast cancer epidemic in Nigerian women","volume":"136","author":"Alatise","year":"2010","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.taap.2014.07.013","article-title":"Arsenic methylation capacity is associated with breast cancer in northern Mexico","volume":"280","author":"Gandolfi","year":"2014","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_56","first-page":"220","article-title":"Genetic polymorphisms of PPAR gamma, arsenic methylation capacity and breast cancer risk in Mexican women","volume":"58","year":"2016","journal-title":"Environ. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.etap.2017.08.032","article-title":"Genetic susceptibility to breast cancer risk associated with inorganic arsenic exposure","volume":"56","author":"Cebrian","year":"2017","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_58","unstructured":"National Center for Biotechnology Information (2020, July 28). ClinVar; [VCV000138289.3], Available online: https:\/\/www.ncbi.nlm.nih.gov\/clinvar\/variation\/VCV000138289.3."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"109361","DOI":"10.1016\/j.envres.2020.109361","article-title":"Inorganic arsenic methylation capacity and breast cancer by immunohistochemical subtypes in northern Mexican women","volume":"184","author":"Gandolfi","year":"2020","journal-title":"Environ. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1093\/oxfordjournals.aje.a008977","article-title":"Toenail trace element levels and breast cancer: A prospective study","volume":"144","author":"Garland","year":"1996","journal-title":"Am. J. Epidemiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1007\/s10552-013-0220-2","article-title":"Dietary arsenic intake and subsequent risk of cancer: The Japan Public Health Center-based (JPHC) Prospective Study","volume":"24","author":"Sawada","year":"2013","journal-title":"Cancer Causes Control."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1002\/ijc.29704","article-title":"Rice consumption and cancer incidence in US men and women","volume":"138","author":"Zhang","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2721","DOI":"10.1002\/ijc.32595","article-title":"Blood arsenic levels and the risk of familial breast cancer in Poland","volume":"146","author":"Marciniak","year":"2019","journal-title":"Int. J. Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1097\/EDE.0000000000000277","article-title":"Residential exposure to estrogen disrupting hazardous air pollutants and breast cancer risk: The California Teachers Study","volume":"26","author":"Liu","year":"2015","journal-title":"Epidemiology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1097\/EDE.0000000000000917","article-title":"Metallic Air Pollutants and Breast Cancer Risk in a Nationwide Cohort Study","volume":"30","author":"White","year":"2019","journal-title":"Epidemiology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"108639","DOI":"10.1016\/j.envres.2019.108639","article-title":"Metallic air pollutants and breast cancer heterogeneity","volume":"177","author":"Kresovich","year":"2019","journal-title":"Environ. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/jes.2013.37","article-title":"Contribution of diet to aggregate arsenic exposures-an analysis across populations","volume":"24","author":"Burgess","year":"2014","journal-title":"J. Expo. Sci. Environ. Epidemiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s13058-019-1168-2","article-title":"Environmental exposures during windows of susceptibility for breast cancer: A framework for prevention research","volume":"21","author":"Terry","year":"2019","journal-title":"Breast Cancer Res."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/11\/3305\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:30:04Z","timestamp":1760178604000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/11\/3305"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,28]]},"references-count":68,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["nu12113305"],"URL":"https:\/\/doi.org\/10.3390\/nu12113305","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,28]]}}}