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Investigating causal relations between sleep traits and risk of breast cancer in women: mendelian randomisation study.

Richmond et al,

2019

BMJ

A Mendelian randomization study using UK Biobank data (156,848 women including 7,784 breast cancer cases) and Breast Cancer Association Consortium data (122,977 cases, 105,974 controls) examined causal effects of sleep traits on breast cancer risk using genetic variants associated with chronotype, sleep duration, and insomnia symptoms. Two-sample MR analysis confirmed that morning preference reduced breast cancer risk by 12% per category increase (OR = 0.88; 95% CI: 0.82-0.93) and provided suggestive evidence that each additional hour of sleep duration increased risk by 19% (OR = 1.19; 95% CI: 1.02-1.39) for both ER+ and ER- breast cancer subtypes, with inconsistent evidence for insomnia symptoms. These findings—robust to sensitivity analyses accounting for horizontal pleiotropy—provide genetic evidence that being a “morning person” may protect against breast cancer while longer sleep duration may increase risk, suggesting that circadian rhythm patterns and sleep duration represent modifiable risk factors, though the counterintuitive finding regarding sleep duration requires further investigation given that adequate sleep is generally considered health-protective.

Health risks of chemicals in consumer products: A review.

Li et al,

2019

Environ Int

A systematic review of 342 peer-reviewed articles covering 202 unique chemicals used in consumer products analyzed exposure pathways, functional uses, product applications, exposure routes, and associated health risks, finding that phthalates, bisphenol-A, and polybrominated diphenyl ethers were the most frequently studied chemicals, with frequently reported uses including plasticizers, polymers/monomers, and flame retardants in food contact materials, personal care products, cosmetics, furniture, flooring, and electronics. The analysis revealed that publication volume on chemicals tends to surge following major regulatory changes or exposure incidents rather than before market introduction, indicating a reactive rather than proactive approach to chemical safety assessment. These findings highlight the critical gap between the increasingly diverse array of chemicals used in consumer products and our lagging understanding of their exposure pathways and human health risks, emphasizing the urgent need to develop capacity and mechanisms for identifying health risks prior to chemical releases rather than after exposure incidents or regulatory action, to enable preventive rather than reactive public health protection.

Night Shift Work and Risk of Breast Cancer in Women.

Bustamante-Montes et al,

2019

Arch Med Res

A case-control study of 101 incident breast cancer cases and 101 matched controls at the Instituto de Seguridad Social del Estado de México y Municipios found that women who worked night shifts had 8.58-fold higher odds of breast cancer compared to those who never worked nights (OR=8.58; 95% CI: 2.19-33.8), while breastfeeding was protective (OR=0.12; 95% CI: 0.02-0.60) and early menarche ≤12 years increased risk (OR=18.58; 95% CI: 2.19-148). Despite the small sample size yielding wide confidence intervals, these findings from Mexican women are consistent with studies from other countries positively associating night shift work with breast cancer risk. The results support the hypothesis that night shift work involving circadian disruption increases breast cancer risk, though the large effect size and wide confidence intervals suggest the need for larger studies with more precise estimates to confirm these associations in Mexican populations.

Environmental chemicals and breast cancer: An updated review of epidemiological literature informed by biological mechanisms.

Rodgers et al,

2018

Environ Res

A systematic review of 158 studies examining environmental chemicals and breast cancer found the strongest evidence for increased risk from exposures during critical developmental periods (in utero, adolescence, pregnancy) to DDT, dioxins, PFOSA, air pollution, and occupational solvents, with risk estimates ranging from 1.4 to 5 times higher. A landmark 50-year study that captured DDT exposure during windows of breast development showed particularly elevated risks, while research on genetic variations found that women with certain DNA repair gene variants had higher breast cancer risk from PAH (polycyclic aromatic hydrocarbon) exposure. However, most studies failed to assess exposure timing during biologically relevant windows of susceptibility, and many current-use chemicals in consumer products remain inadequately studied, with major challenges including reconstructing decades-old exposures and measuring rapidly metabolized chemicals in complex real-world mixtures.

Lifetime exposure to ambient air pollution and methylation of tumor suppressor genes in breast tumors.

Callahan et al,

2018

Environ Res

A study of women from the Western New York Exposures and Breast Cancer Study examined associations between early life air pollution exposure (total suspended particulates and traffic emissions as proxies for polycyclic aromatic hydrocarbons) and DNA methylation of nine genes in breast tumor tissue, finding nominally significant associations including higher TSP at first birth associated with altered SCGB3A1 (OR=0.48) and SYK (OR=1.86) methylation, and traffic emissions at menarche associated with increased SYK methylation (OR=2.37), though none remained significant after multiple comparison adjustment. These preliminary findings provide suggestive evidence that ambient air pollution exposure during critical developmental windows (birth, menarche, first birth) may influence epigenetic methylation patterns of tumor suppressor genes in breast tissue, potentially representing a mechanism linking early life environmental exposures to later breast cancer risk. Larger studies assessing more methylation sites are warranted to confirm whether air pollution exposure during vulnerable life stages causes lasting epigenetic changes that contribute to breast cancer development.

Connecting the dots between breast cancer, obesity and alcohol consumption in middle-aged women: ecological and case control studies.

Miller et al,

2018

BMC Pub Health

A mixed ecological and case-control study in Australia found that obesity occurring between ages 31-40 was independently associated with a 250% increased breast cancer risk in middle-aged women, though no direct association was found between alcohol consumption and breast cancer in the case-control analysis despite ecological correlations. The study revealed that stress was ecologically linked to both alcohol consumption and obesity but not directly to breast cancer incidence, suggesting that stress may influence breast cancer risk indirectly through health behaviors rather than representing a “missing link” as hypothesized. These findings highlight a critical window for breast cancer prevention: obesity in the decade before age 40 appears particularly risky, supporting targeted weight management interventions for women in their 30s, while the complex interrelationships between stress, alcohol, obesity, and breast cancer warrant further investigation using longitudinal designs that can capture temporal sequences and cumulative exposures across women’s reproductive years.

Environmental estrogen-like endocrine disrupting chemicals and breast cancer.

Morgan et al,

2017

Molec Cell Endocrinol

This study examines the role of environmental estrogen-like endocrine-disrupting chemicals (EEDs) in breast cancer development. EEDs are synthetic compounds that mimic estrogen, and the ones being studied in this paper include polychlorinated biphenyls (PCBs), bisphenol A (BPA), and phthalates. The results of the study show that of the EEDs tested, only one type of PCB, PCB138, had a strong association with the formation of breast cancer, where as phthalates (and it metabolites) but and BPA showed no strong correlation. Additionaly, the researchers identify that these EEDs promote the proliferation of breast cancer cells, induce epigenetic changes that may increase susceptibility to cancer, as well as alter developmental pathways during critical windows of breast development.

Tissue accumulation of microplastics in mice and biomarker responses suggest widespread health risks of exposure.

Deng et al,

2017

Sci Rep

An experimental study in mice using fluorescent polystyrene microplastics (5 μm and 20 μm diameter) found that microplastics accumulated in liver, kidney, and gut with tissue distribution and kinetics strongly dependent on particle size. Exposure induced disturbances in energy and lipid metabolism, oxidative stress, and altered blood biomarkers of neurotoxicity, as revealed through biochemical analyses and metabolomic profiling. This study provides new evidence for adverse health consequences of microplastic exposure in mammals, demonstrating tissue-specific accumulation patterns and systemic metabolic disruptions, though information about microplastic toxicity in mammals remains limited compared to marine organisms despite the ubiquitous environmental presence of these particles in oceans, rivers, soil, food, and even table salt.

A review of hair product use on breast cancer risk in African American women.

Stiel et al,

2016

Cancer Med

A review examining breast cancer disparities in African American women—who now have similar incidence rates to non-Hispanic White women but significantly higher mortality—found growing evidence linking hair product use to breast cancer risk through exposure to estrogen-like chemicals and endocrine-disrupting chemicals (EDCs). The review identified three converging lines of evidence: environmental estrogen and EDC exposures increase breast cancer risk, these chemicals are present in personal care products including hair products, and certain hair products used disproportionately by African American women may contribute to elevated breast cancer risk in this population. The findings highlight an understudied environmental justice issue and call for additional research using community-collaborative approaches to better understand how culturally specific beauty practices may contribute to health disparities, representing what researchers term the potential “cost of beauty.”

Environmental immune disruptors, inflammation and cancer risk.

Thompson et al,

2015

Carcinogenesis

A review examining the intersection of environmental toxicants, immune function, and cancer development argues that common chemicals like bisphenol A, atrazine, and phthalates can disrupt the delicate balance between pro- and anti-inflammatory immune responses, potentially contributing to tumor development through immune system dysfunction. The authors highlight that while the role of immunity in cancer is well-established, research on how environmental chemicals affect immune cells as co-factors in cancer causation remains underdeveloped compared to studies on autoimmunity and allergies. The review calls for increased research using systems biology approaches to better understand how chemical exposures disturb inflammatory pathways and immune molecules involved in tumor-associated inflammation, arguing that chemically induced immune perturbations represent an important but understudied mechanism of environmental carcinogenesis.

Disruptive environmental chemicals and cellular mechanisms that confer resistance to cell death.

Narayanan et al,

2015

Carcinogenesis

This study explores the linkage between environmental chemical exposures and cellular resistance to cell death, a carcinogenic trait. The researchers in this study specifically investigate BPA, chlorothalonil, dibutyl phthalate, and more because of their disruptive effects that may be involved in these carcinogenic pathways. The researchers found that arsenic interferes with cellular signaling pathways and induces oxidative stress, leading to impaired apoptosis; dioxins bind to aryl hydrocarbon receptors (AHRs), which alters gene expression and disrupts normal cell death processes; BPA mimics the estrogen hormone, affecting hormonal balance and promoting cell survival pathways that inhibit cell death. By allowing cells to evade cell death, these environmental chemicals can promote the survival of cells with genetic mutations and therefore increase the risk of cancer development.

Caramel Color in Soft Drinks and Exposure to 4-Methylimidazole: A Quantitative Risk Assessment

Smith et al,

2015

PLOS One

A recent study investigated the potential carcinogen 4-methylimidazole (4-MEI) in popular beverages colored with caramel, revealing potential cancer risks. Using data from California, where Proposition 65 enforces warning labels on drinks exceeding safe 4-MEI levels, researchers found that 4-MEI concentrations varied by brand and region. For example, Malta Goya had the highest 4-MEI levels, while Coca-Cola had the lowest. Regular consumption of certain sodas could result in daily 4-MEI exposure above safe limits.

Early-life Exposure to Endocrine Disrupting Chemicals and Later-life Health Outcomes: An Epigenetic Bridge?

Vaiserman et al,

2014

Aging Dis

The following review article described how exposure to EDCs during early development can lead to adverse health outcomes later in life through epigenetic mechanisms based on existing studies. The article emphasizes that exposure to EDCs during critical developmental periods such as in utero and early childhood, can have lasting effects on health since, during these periods, the body’s systems are particularly vulnerable to exposures. Additionally, the article finds a link between early-life exposure to EDCs and increased risk of various health issues later on in life, including metabolic disorders and cancers. The suspected mechanism by which these chemicals do this is thought to be mediated by epigenetic changes, which are changes to gene expression without altering the DNA. Therefore, the article emphasizes understanding how exposure during such sensitive periods in development can pose such drastic problems later on in life.

New exposure biomarkers as tools for breast cancer epidemiology, biomonitoring, and prevention: a systematic approach based on animal evidence.

Rudel et al,

2014

Environ Health Perspect

This review of exposure biomarkers for chemicals potentially linked to breast cancer identified methods for 102 chemicals causing mammary tumors in rodents, finding biomarkers for nearly 75% of them, with human exposure biomarkers existing for 62 chemicals (45 measured in non-occupationally exposed populations) and the CDC tracking 23 of them. Among rodent mammary carcinogens with >50% population detection frequency were PAHs (98%), methyleugenol (98%), PFOA (>50%), chlordane (>50%), acrylamide (>50%), and benzene (>50%), indicating near-universal exposure to multiple mammary carcinogens, with several additional chemicals showing >50% detection of urinary metabolites including ethylene oxide, acrylonitrile, fenvalerate, and vinyl chloride (71-75%). The study found consistent carcinogenicity between humans and rodents for many chemicals, though limited data exists for direct effects in humans, and emphasizes the availability of biomonitoring tools and resources to advance breast cancer prevention efforts. The findings underscore that populations are ubiquitously exposed to multiple known mammary carcinogens simultaneously, highlighting the urgent need for biomonitoring programs to assess mixed exposures and inform prevention strategies targeting modifiable environmental risk factors for breast cancer.

Endocrine disruptors and asthma-associated chemicals in consumer products.

Dodson et al,

2012

Environ Health Perspect

This study analyzed 213 everyday products, including cosmetics, cleaners, and personal care items, for endocrine-disrupting chemicals (EDCs) and asthma-related compounds. Testing revealed 55 chemicals, with fragranced products and sunscreens containing the highest levels. Vinyl products were also found to contain significant amounts of bis(2-ethylhexyl) phthalate (DEHP), a known EDC. Many harmful chemicals were not listed on product labels, limiting consumer ability to avoid them. These results highlight the presence of potentially harmful chemicals in commonly used products, raising concerns about their widespread use in household and personal care items.

Heavy metals and phthalate contamination in prenatal vitamins and folic acid supplements

Gardener et al.

2025

Environ Res

A study analyzing 156 commercially available prenatal vitamins, 19 folate/folic acid supplements, and 9 prescription prenatals found widespread contamination with heavy metals and phthalates: 83% of commercial prenatals contained detectable lead (15% exceeding California’s 0.5 μg/daily threshold), 73% contained cadmium, 25% contained DEHP, and 13% contained DBP, with higher contamination associated with calcium and iron content and caplet/capsule/tablet formulations. Prescription prenatals also showed contamination, with 7 of 9 containing detectable lead or cadmium and 33% exceeding the lead threshold, while folate/folic acid supplements showed lower contamination levels. These findings reveal that pregnant women—a population particularly vulnerable to environmental chemical exposures—are being exposed to lead, cadmium, and endocrine-disrupting phthalates through the very supplements intended to support healthy pregnancy. Since prenatal supplementation remains critical for fetal development, pregnant women should prioritize products with third-party verification seals (such as USP, NSF International, or ConsumerLab) which confirm label accuracy, purity, and manufacturing standards, and clear, enforceable regulations requiring frequent testing and strict contamination limits are urgently needed.

Surveillance and dietary risk assessment of endocrine-disrupting pesticides in eggplant/brinjal and cauliflower in Pakistan.

Talat et al,

2023

Environ Sci Poll Res

A study of vegetables sold in Pakistan found that 80% of eggplant and 69% of cauliflower samples were contaminated with endocrine-disrupting pesticides, with 20% of eggplant exceeding EU safety limits and particularly high levels of chlorpyrifos (an androgen blocker) and cyhalothrin-lambda (a thyroid hormone inhibitor). The acute health risk from eating contaminated cauliflower exceeded safe limits by more than 200% for both men and women, meaning a single serving could deliver more than twice the acceptable daily dose of these hormone-disrupting chemicals. While estimated long-term (chronic) health risks were low for most population groups, the high acute exposure is concerning because these pesticides can interfere with hormone function and potentially increase risks for hormone-related diseases like breast cancer, especially with repeated exposures over time.

A comprehensive assessment of endocrine-disrupting chemicals in an Indian food basket: Levels, dietary intakes, and comparison with European data.

Sharma et al,

2021

Environ Pollut

A study comparing endocrine-disrupting chemical (EDC) contamination in Indian food found that while all tested foods—especially dairy and meat—contained organochlorine pesticides, PCBs, PBDEs, and dioxins, overall dietary exposure levels were comparable to or lower than those in Europe despite weaker regulations in India. Urban Delhi markets had higher contamination than peri-urban areas, with organochlorine pesticides being the primary contaminants, yet Indians’ lower meat consumption meant their total EDC exposure was similar to Europeans’ despite some European foods having higher chemical residues. The findings highlight that EDC contamination is a global food system issue driven by international trade of food and animal feed, underscoring the need for internationally harmonized standards on EDC limits in food to protect public health worldwide, as chemical exposures that increase risks for diseases like breast cancer cross borders through the global food supply.

Cohort profile: Norwegian offshore Petroleum workers (Nopw) cohort

Stenehjem et al,

2020

Epidemiol

This study of Norwegian offshore petroleum workers found that both male and female workers had increased overall cancer risk (7% and 13% increased risk, respectively), with particularly notable elevations for specific cancers. Male workers showed more than double the risk of pleural cancer (138% increase) and male breast cancer (118% increase), plus a 20% increased risk of prostate cancer, while female workers had 62% increased risk of melanoma and nearly quadruple the risk of acute myeloid leukemia (276% increase). These findings suggest that occupational exposures in the offshore petroleum industry—including potential exposure to chemicals, radiation, shift work, and other workplace hazards—may contribute to elevated cancer risks across multiple organ sites in both men and women.

Low dose bisphenol S or ethinyl estradiol exposures during the perinatal period alter female mouse mammary gland development.

Kolla et al,

2018

Reprod Toxicol

A developmental toxicology study exposed CD-1 mice to bisphenol S (BPS) at 2 or 200 μg/kg/day or ethinyl estradiol (EE2) at 0.01 or 1 μg/kg/day during pregnancy and lactation, then examined mammary glands of female offspring at three developmental stages (pre-puberty, puberty, and early adulthood) for growth parameters, histopathology, cell proliferation, and hormone receptor expression. The study revealed age- and dose-specific effects of BPS on mammary gland development that differed from both EE2 effects and previously reported bisphenol A (BPA) effects. These findings suggest that individual xenoestrogens—synthetic chemicals with hormonal activities—may have unique effects on mammary tissue development, supporting the hypothesis that endocrine-disrupting chemicals could contribute to breast diseases and dysfunction through disruption of normal mammary gland development, though each compound may act through distinct mechanisms.

Pharmaceuticals and endocrine disruptors in raw and cooked seafood from European market: Concentrations and human exposure levels.

Álvarez-Muñoz et al,

2018

Environ Int

A study analyzing 65 seafood samples (195 analyses including raw and cooked preparations) from 11 European countries for pharmaceuticals (PhACs) and endocrine-disrupting compounds (EDCs)—chemicals linked to reproductive system effects, metabolic disorders, breast cancer pathogenesis, and antimicrobial resistance—found that while pharmaceuticals were mostly undetectable, EDCs were quantified in the majority of samples, with cooking by steaming significantly increasing their levels 2- to 46-fold. Human exposure assessment focused on three prevalent EDCs (bisphenol A, methylparaben, and triclosan) revealed that the Spanish population had the highest exposure through seafood consumption among the 11 countries studied, though exposures remained below current toxicological reference values. These findings highlight that commercially available seafood in the European Union market contains detectable levels of endocrine-disrupting contaminants that concentrate during cooking, raising concerns about cumulative dietary exposure to these compounds through this widely consumed protein source, particularly in populations with high seafood consumption patterns.

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: focus on the cancer hallmark of tumor angiogenesis.

Hu et al,

2015

Carcinogenesis

This paper examined how low doses of environmental chemical mixtures may contribute to cancer development by promoting tumor angiogenesis, and the formation of new blood vessels that supply nutrients to tumors. The authors identified chemicals that may interfere with these angiogenic pathways, such as those involving vascular endothelial growth factor (VEGF) and hypoxia-inducible factors (HIFs). Chemicals disrupting these pathways can lead to uncontrolled blood vessel formation in tumors. However, there is a need for further research to understand the combined effects of low-dose chemical exposures on angiogenesis and cancer risk.

Environmental pollutants and breast cancer: epidemiologic studies.

Brody et al,

2007

Cancer

A comprehensive review found that while laboratory studies have identified numerous environmental chemicals that cause breast tumors in animals or mimic estrogen, human epidemiological evidence is strongest for PAHs (found in air pollution and grilled foods) and PCBs (banned industrial chemicals), particularly in women with certain genetic variations affecting how their bodies process these chemicals and hormones. Evidence linking dioxins and organic solvents to breast cancer is limited but suggestive, while many chemicals identified as mammary carcinogens in animal studies have never been investigated in human populations due to challenges in measuring past exposures and the decades-long delay between exposure and cancer diagnosis. The review argues that given these methodological limitations in human studies, policymakers should rely more heavily on animal and laboratory evidence to develop regulations that reduce chemical exposures, as waiting for definitive human proof may unnecessarily delay prevention strategies that could reduce breast cancer rates.

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