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Persistent Organic Pollutants and Breast Cancer: A Systematic Review and Critical Appraisal of the Literature.

ABSTRACT: Persistent organic pollutants (POPs) bioaccumulate in the food chain and have been detected in human blood and adipose tissue. Experimental studies demonstrated that POPs can cause and promote growth of breast cancer. However, inconsistent results from epidemiological studies do not support a causal relationship between POPs and breast cancer in women. To identify individual POPs that are repeatedly found to be associated with both breast cancer incidence and progression, and to demystify the observed inconsistencies between epidemiological studies, we conducted a systematic review of 95 studies retrieved from three main electronic databases. While no clear pattern of associations between blood POPs and breast cancer incidence could be drawn, POPs measured in breast adipose tissue were more clearly associated with higher breast cancer incidence. POPs were more consistently associated with worse breast cancer prognosis whether measured in blood or breast adipose tissue. In contrast, POPs measured in adipose tissue other than breast were inversely associated with both breast cancer incidence and prognosis. Differences in biological tissues used for POPs measurement and methodological biases explain the discrepancies between studies results. Some individual compounds associated with both breast cancer incidence and progression, deserve further investigation.

SUBMITTER: Ennour-Idrissi K

PROVIDER: S-EPMC6721417 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Persistent Organic Pollutants and Breast Cancer: A Systematic Review and Critical Appraisal of the Literature.

Ennour-Idrissi Kaoutar K Ayotte Pierre P Diorio Caroline C

Cancers 20190727 8

Persistent organic pollutants (POPs) bioaccumulate in the food chain and have been detected in human blood and adipose tissue. Experimental studies demonstrated that POPs can cause and promote growth of breast cancer. However, inconsistent results from epidemiological studies do not support a causal relationship between POPs and breast cancer in women. To identify individual POPs that are repeatedly found to be associated with both breast cancer incidence and progression, and to demystify the ob ...[more]

PMID: 31357644

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Project description:BackgroundDespite increasing regulation, exposure to persistent organic pollutants (POPs) remains a serious public health concern due to their accumulation in the environment and ability to biomagnify up the food chain. POPs are associated with endocrine-disrupting effects including adverse reproductive outcomes that could affect fecundability, i.e. the capacity to conceive a pregnancy, quantified as time to pregnancy (TTP).Objective and rationaleResults of epidemiologic studies that examine the impact of various chemical classes of POPs on TTP have not been synthesised. We undertook a systematic review to summarise the strength of evidence for associations of four common groups of POPs with couple fecundability and to identify gaps and limitations in the literature in order to inform policy decisions and future research.Search methodsWe performed an electronic search of literature published between 1 January 2007 and 6 August 2019 in MEDLINE, EMBASE.com, Global Health, DART/TOXLINE and POPLINE. We included empirical research papers that examined human exposure to organochlorine (OC) pesticides, brominated flame retardants, polychlorinated organic compounds and/or per- and polyfluoroalkyl substances (PFAS) and considered TTP or fecundability as an outcome. Standardised forms for screening, data extraction and study quality were developed using DistillerSR software, and all reviews were completed in duplicate. We used the Newcastle-Ottawa Scale to assess risk of bias and devised additional quality metrics based on specific methodological features of fecundability studies.OutcomesThe search returned 4573 articles, and 28 papers from 19 different studies met inclusion criteria. Among them, four studies measured TTP prospectively, three had data on participants' prenatal exposure, three examined associations in both male and female partners and one focused exclusively on males. Analyses varied widely in terms of exposure characterisation, precluding a meta-analytic approach. Evidence was strongest for adverse associations of female exposure to polychlorinated biphenyls with TTP, with some additional support for associations of female exposure to polybrominated diphenyl ethers and PFAS with longer TTP. Our review provided little or no support for associations between female exposure to OC pesticides or male exposure to any of the POP groups and TTP.Wider implicationsEvidence suggests that female exposure to at least some POPs may reduce fecundability. Although many of these chemicals are no longer in production, they are still detectable in human biosamples because of their persistence in the environment. Replacement chemicals that are being introduced as older ones are restricted may have similar reproductive consequences. Future studies should examine these newer POPs, assess interactions between POPs and other chemical and non-chemical exposures, investigate how POPs are distributed in and metabolised by the human body and focus on populations that may be disproportionately exposed.

Project description:Objective: This work aims to systematically identify, describe, and appraise all prognostic models for cervical cancer and provide a reference for clinical practice and future research. Methods: We systematically searched PubMed, EMBASE, and Cochrane library databases up to December 2020 and included studies developing, validating, or updating a prognostic model for cervical cancer. Two reviewers extracted information based on the CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modeling Studies checklist and assessed the risk of bias using the Prediction model Risk Of Bias ASsessment Tool. Results: Fifty-six eligible articles were identified, describing the development of 77 prognostic models and 27 external validation efforts. The 77 prognostic models focused on three types of cervical cancer patients at different stages, i.e., patients with early-stage cervical cancer (n = 29; 38%), patients with locally advanced cervical cancer (n = 27; 35%), and all-stage cervical cancer patients (n = 21; 27%). Among the 77 models, the most frequently used predictors were lymph node status (n = 57; 74%), the International Federation of Gynecology and Obstetrics stage (n = 42; 55%), histological types (n = 38; 49%), and tumor size (n = 37; 48%). The number of models that applied internal validation, presented a full equation, and assessed model calibration was 52 (68%), 16 (21%), and 45 (58%), respectively. Twenty-four models were externally validated, among which three were validated twice. None of the models were assessed with an overall low risk of bias. The Prediction Model of Failure in Locally Advanced Cervical Cancer model was externally validated twice, with acceptable performance, and seemed to be the most reliable. Conclusions: Methodological details including internal validation, sample size, and handling of missing data need to be emphasized on, and external validation is needed to facilitate the application and generalization of models for cervical cancer.

Project description:Exposure to persistent organic pollutants (POPs), such as dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCBs), has historically been linked to population collapses in wildlife. Despite international regulations, these legacy chemicals are still currently detected in women of reproductive age, and their levels correlate with reduced ovarian reserve, longer time-to-pregnancy, and higher risk of infertility. However, the specific modes of action underlying these associations remain unclear. Here, we examined the effects of five commonly occurring POPs − hexachlorobenzene (HCB), p,p'-dichlorodiphenyldichloroethylene (DDE), 2,3,3′,4,4′,5-hexachlorobiphenyl (PCB156), 2,2′,3,4,4′,5,5′-heptachlorobiphenyl (PCB180), perfluorooctane sulfonate (PFOS) − and their mixture on human ovaries in vitro. We exposed human ovarian cancer cell lines COV434, KGN, and PA1 as well as primary ovarian cells for 24 h, and ovarian tissue containing unilaminar follicles for 6 days. RNA-sequencing of samples exposed to concentrations covering epidemiologically relevant levels revealed significant gene expression changes related to central energy metabolism in the exposed cells, indicating glycolysis, oxidative phosphorylation, fatty acid metabolism, and reactive oxygen species as potential shared targets of POP exposures in ovarian cells. Alpha-enolase (ENO1), lactate dehydrogenase A (LDHA), cytochrome C oxidase subunit 4I1 (COX4I1), ATP synthase F1 subunit alpha (ATP5A), and glutathione peroxidase 4 (GPX4) were validated as targets through qPCR in additional cell culture experiments in KGN. In ovarian tissue cultures, we observed significant effects of exposure on follicle growth and atresia as well as protein expression. All POP exposures, except PCB180, decreased unilaminar follicle proportion and increased follicle atresia. Immunostaining confirmed altered expression of LDHA, ATP5A, and GPX4 in the exposed tissues. Moreover, POP exposures modified ATP production in KGN and tissue culture. In conclusion, our results demonstrate the disruption of cellular energy metabolism as a novel mode of action underlying POP-mediated interference of follicle growth in human ovaries.

Dataset Information

Persistent Organic Pollutants and Breast Cancer: A Systematic Review and Critical Appraisal of the Literature.

Publications

Persistent Organic Pollutants and Breast Cancer: A Systematic Review and Critical Appraisal of the Literature.

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