Dataset Information

Environmental exposures and breast cancer risk in the context of underlying susceptibility: A systematic review of the epidemiological literature.

ABSTRACT:

Background

The evidence evaluating environmental chemical exposures (ECE) and breast cancer (BC) risk is heterogeneous which may stem in part as few studies measure ECE during key BC windows of susceptibility (WOS). Another possibility may be that most BC studies are skewed towards individuals at average risk, which may limit the ability to detect signals from ECE.

Objectives

We reviewed the literature on ECE and BC focusing on three types of studies or subgroup analyses based on higher absolute BC risk: BC family history (Type 1); early onset BC (Type 2); and/or genetic susceptibility (Type 3).

Methods

We systematically searched the PubMed database to identify epidemiologic studies examining ECE and BC risk published through June 1, 2019.

Results

We identified 100 publications in 56 unique epidemiologic studies. Of these 56 studies, only 2 (3.6%) were enriched with BC family history and only 11% of studies (6/56) were specifically enriched with early onset cases. 80% of the publications from these 8 enriched studies (Type 1: 8/10 publications; Type 2: 8/10 publications) supported a statistically significant association between ECE and BC risk including studies of PAH, indoor cooking, NO₂, DDT; PCBs, PFOSA; metals; personal care products; and occupational exposure to industrial dyes. 74% of Type 3 publications (20/27) supported statistically significant associations for PAHs, traffic-related air pollution, PCBs, phthalates, and PFOSAs in subgroups of women with greater genetic susceptibility due to variants in carcinogen metabolism, DNA repair, oxidative stress, cellular apoptosis and tumor suppressor genes.

Discussion

Studies enriched for women at higher BC risk through family history, younger age of onset and/or genetic susceptibility consistently support an association between an ECE and BC risk. In addition to measuring exposures during WOS, designing studies that are enriched with women at higher absolute risk are necessary to robustly measure the role of ECE on BC risk.

SUBMITTER: Zeinomar N

PROVIDER: S-EPMC7314105 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BACKGROUND:The long time from exposure to potentially harmful chemicals until breast cancer occurrence poses challenges for designing etiologic studies and for implementing successful prevention programs. Growing evidence from animal and human studies indicates that distinct time periods of heightened susceptibility to endocrine disruptors exist throughout the life course. The influence of environmental chemicals on breast cancer risk may be greater during several windows of susceptibility (WOS) in a woman's life, including prenatal development, puberty, pregnancy, and the menopausal transition. These time windows are considered as specific periods of susceptibility for breast cancer because significant structural and functional changes occur in the mammary gland, as well as alterations in the mammary micro-environment and hormone signaling that may influence risk. Breast cancer research focused on these breast cancer WOS will accelerate understanding of disease etiology and prevention. MAIN TEXT:Despite the plausible heightened mechanistic influences of environmental chemicals on breast cancer risk during time periods of change in the mammary gland's structure and function, most human studies of environmental chemicals are not focused on specific WOS. This article reviews studies conducted over the past few decades that have specifically addressed the effect of environmental chemicals and metals on breast cancer risk during at least one of these WOS. In addition to summarizing the broader evidence-base specific to WOS, we include discussion of the NIH-funded Breast Cancer and the Environment Research Program (BCERP) which included population-based and basic science research focused on specific WOS to evaluate associations between breast cancer risk and particular classes of endocrine-disrupting chemicals-including polycyclic aromatic hydrocarbons, perfluorinated compounds, polybrominated diphenyl ethers, and phenols-and metals. We outline ways in which ongoing transdisciplinary BCERP projects incorporate animal research and human epidemiologic studies in close partnership with community organizations and communication scientists to identify research priorities and effectively translate evidence-based findings to the public and policy makers. CONCLUSIONS:An integrative model of breast cancer research is needed to determine the impact and mechanisms of action of endocrine disruptors at different WOS. By focusing on environmental chemical exposure during specific WOS, scientists and their community partners may identify when prevention efforts are likely to be most effective.

Project description:Epigenetic control of gene transcription is critical for normal human development and cellular differentiation. While alterations of epigenetic marks such as DNA methylation have been linked to cancers and many other human diseases, interindividual epigenetic variations in normal tissues due to aging, environmental factors, or innate susceptibility are poorly characterized. The plasticity, tissue-specific nature, and variability of gene expression are related to epigenomic states that vary across individuals. Thus, population-based investigations are needed to further our understanding of the fundamental dynamics of normal individual epigenomes. We analyzed 217 non-pathologic human tissues from 10 anatomic sites at 1,413 autosomal CpG loci associated with 773 genes to investigate tissue-specific differences in DNA methylation and to discern how aging and exposures contribute to normal variation in methylation. Methylation profile classes derived from unsupervised modeling were significantly associated with age (P<0.0001) and were significant predictors of tissue origin (P<0.0001). In solid tissues (n = 119) we found striking, highly significant CpG island-dependent correlations between age and methylation; loci in CpG islands gained methylation with age, loci not in CpG islands lost methylation with age (P<0.001), and this pattern was consistent across tissues and in an analysis of blood-derived DNA. Our data clearly demonstrate age- and exposure-related differences in tissue-specific methylation and significant age-associated methylation patterns which are CpG island context-dependent. This work provides novel insight into the role of aging and the environment in susceptibility to diseases such as cancer and critically informs the field of epigenomics by providing evidence of epigenetic dysregulation by age-related methylation alterations. Collectively we reveal key issues to consider both in the construction of reference and disease-related epigenomes and in the interpretation of potentially pathologically important alterations.

Project description:PurposeRecent evidence suggests a global burden of chronic cough in general populations. However, the definitions vary greatly among epidemiological studies, and none have been validated for clinical relevance. We aimed to examine previous epidemiological definitions in detail and explore the operational characteristics.MethodsA systematic review was conducted for epidemiological surveys that reported the prevalence of chronic cough in general adult populations during the years 1980 to 2013. A literature search was performed on Pubmed and Embase without language restriction. Epidemiological definitions for chronic cough were classified according to their components, such as cutoff duration. Meta-analyses were performed for the male-to-female ratio of chronic cough prevalence to explore operational characteristics of epidemiological definitions.ResultsA total of 70 studies were included in the systematic review. The most common epidemiological definition was identified as 'cough ≥3 months' duration without specification of phlegm (n=50); however, it conflicted with the cutoff duration in current clinical guidelines (cough ≥8 weeks). Meta-analyses were performed for the male-to-female ratio of chronic cough among 28 studies that reported sex-specific prevalence using the most common definition. The pooled male-to-female odds ratio was 1.26 (95% confidence interval 0.92-1.73) with significant heterogeneity (I²=96%, P<0.001), which was in contrast to clinical observations of female predominance from specialist clinics. Subgroup analyses did not reverse the ratio or reduce the heterogeneity.ConclusionsThis study identified major issues in defining chronic cough in future epidemiological studies. The conflict between epidemiological and clinical diagnostic criteria needs to be resolved. The unexpected difference in the gender predominance between the community and clinics warrants further studies. Clinical validation of the existing definition is required.

Project description:Objectives: To carry out an integrated and stratified meta-analysis on occupational exposure to electromagnetic fields (EMFs), metals and pesticides and its effects on amyotrophic lateral sclerosis (ALS) and Parkinson's and Alzheimer's disease, and investigate the possibility of publication bias. Methods: In the current study, we updated our recently published meta-analyses on occupational exposures in relation to ALS, Alzheimer's and Parkinson's disease. Based on 66 original publications of good scientific epidemiological standard, according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines, we analysed subgroups by carrying out stratified meta-analyses on publication year, statistical precision of the relative risk (RR) estimates, inspection of the funnel plots and test of bias. Results: Based on 19 studies the weighted RR for occupational exposure to EMFs was 1.26 (95% confidence interval (CI) 1.07?1.50) for ALS, 1.33 (95% CI 1.07?1.64) for Alzheimer's disease and 1.02 (95% CI 0.83?1.26) for Parkinson's disease. Thirty-one studies concerned occupational exposure to pesticides and the weighted RR was 1.35 (95% CI 1.02?1.79) for ALS, 1.50 (95% CI 0.98?2.29) for Alzheimer's disease and 1.66 (95% CI 1.42?1.94) for Parkinson's disease. Finally, 14 studies concerned occupational exposure to metals and only exposure to lead (five studies) involved an elevated risk for ALS or Parkinson's disease and the weighted RR was 1.57 (95% CI 1.11?2.20). The weighted RR for all the non-lead exposures was 0.97 (95% CI 0.88?1.06). Conclusions: Exposure to pesticides increased the risk of getting the mentioned neurodegenerative diseases by at least 50%. Exposure to lead was only studied for ALS and Parkinson's disease and involved 50% increased risk. Occupational exposure to EMFs seemed to involve some 10% increase in risk for ALS and Alzheimer's disease only.