Serum and adipose tissue as matrices for assessment of exposure to persistent organic pollutants in breast cancer patients

Artacho‐Cordón, Francisco; Fernández-Rodríguez, María; Garde, Christian; Elena, Salamanca,; Iribarne-Durán, L.M.; Torné, Pablo; Expósito, José; Papay-Ramírez, L.; Fernández, Mariana F.; Olea, Nicolás; Arrebola, Juan Pedro

doi:10.1016/j.envres.2015.08.020

Cited by 57 publications

(21 citation statements)

References 65 publications

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“…Furthermore, we used the serum measurements as indicator of breast tissue exposure. Preferably, the concentration should have been measured in the adipose tissue; however, studies have reported that serum levels of the lipophilic POPs are highly correlated with the level in breast tissue [52, 53]. Using serum POP levels appears to be a reasonable biomarker for long-term exposure.…”

Section: Discussionmentioning

confidence: 99%

Serum levels of environmental pollutants is a risk factor for breast cancer in Inuit: a case control study

2017

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BackgroundEnvironmental Persistent Organic Pollutants (POPs) can alter the hormone homeostasis by mimicking, interfering or blocking the function of hormones; moreover POPs are hypothesized to modify the risk of breast cancer. The association between POPs and breast cancer has been widely studied but the conclusions are inconsistent. The present study examined the associations between serum levels of POPs and breast cancer with focus on the highly exposed Greenlandic Inuit population.MethodsThe study design was a case-control study of Inuit women from Greenland. The participants were asked to complete a questionnaire with information on reproductive history and lifestyle and to provide a blood sample. The sampling was carried out in two time periods (2000–2003 and 2011–2014). The serum levels were determined of 14 polychlorinated biphenyls (PCBs), 11 organochlorine pesticides (OCPs), 16 perfluoroalkyl acids (PFAAs), 1 polybrominated biphenyl (PBB), and 9 polybrominated diphenyl ethers (PBDEs). Independent samples t-test was used to compare differences between cases and controls and odds ratios (OR) adjusted for identified confounders were obtained using logistic regression.ResultsThe study population included 77 breast cancer cases and 84 controls. The majority of the measured compounds declined significantly from 2000 – 2003 to 2011–2014. However, for the perfluorinated carboxylic acids (PFCAs) an increase was observed. The serum levels were significantly higher in cases compared to controls for the majority of the compounds, and after adjusting for age the difference was maintained for ∑OCP, dichlorodiphenyldichloroethylene (p,p′-DDE), ∑PFAA, ∑perfluorinated sulfonic acids (PFSA), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS). For the lipophilic POPs, high serum levels (middel/highest vs. lowest tertile) of ∑PCB, ∑estrgoenicPCB, PCB99, PCB138, PCB153, PCB170, PCB170, and PCB183 was associated with breast cancer risk; for the amphiphilic PFAAs, high serum levels of ∑PFAA, ∑PFCA, ∑PFSA, perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), PFHxS, and PFOS were associated with breast cancer risk.ConclusionSignificant, positive associations between breast cancer risk and PCBs and PFAAs were observed. The associations indicate that environmental exposure to POPs can be a factor increasing the risk for breast cancer in Inuit women.Electronic supplementary materialThe online version of this article (doi:10.1186/s12940-017-0269-6) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Serum levels of environmental pollutants is a risk factor for breast cancer in Inuit: a case control study

2017

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“…Given the highly lipophilic nature of the OC compounds, especially those presently utilized, tissue bioaccumulation over time in lipid rich tissues would be expected to exceed serum levels. Depending on the study population, the adipose to serum ratios based on lipid adjusted values for DDE have been shown to range from 1.9 to 3.9 indicating significant adipose accumulation . While most biomonitoring studies have utilized serum and to a lesser extend adipose tissue OC levels, there is a relative lack of studies examining hepatic levels of many OC compounds, especially trans‐nonachlor.…”

Section: Discussionmentioning

confidence: 99%

Alterations in cellular lipid metabolism produce neutral lipid accumulation following exposure to the organochlorine compound trans‐nonachlor in rat primary hepatocytes

Howell

McDevitt

Henein

et al. 2018

Environmental Toxicology

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Recent epidemiological studies have revealed significant positive associations between exposure to organochlorine (OC) pesticides and occurrence of the metabolic syndrome and there are a growing number of animal-based studies to support causality. However, the cellular mechanisms linking OC compound exposure and metabolic dysfunction remain elusive. Therefore, the present study was designed to determine if direct exposure to three highly implicated OC compounds promoted hepatic steatosis, the hepatic ramification of the metabolic syndrome. First, the steatotic effect of p,p'-dichlorodiphenyldichloroethylene (DDE), oxychlordane, and trans-nonachlor was determined in freshly isolated rat primary hepatocytes. Exposure to trans-nonachlor significantly increased neutral lipid accumulation as opposed to DDE and oxychlordane. To determine possible mechanisms governing increased fatty acid availability, the effects of trans-nonachlor exposure on fatty acid uptake, de novo lipogenesis, triglyceride secretion, and fatty acid oxidation were explored. Trans-nonachlor did not significantly alter fatty acid uptake. However, insulin-stimulated de novo lipogenesis as well as basal expression of fatty acid synthase, a major regulator of lipogenesis were significantly increased following trans-nonachlor exposure. Interestingly, there was a significant decrease in fatty acid oxidation following trans-nonachlor exposure. This decrease in fatty acid oxidation was accompanied by a slight, but significant increase in oleic acid-induced cellular triglyceride secretion. Therefore, taken together, the present data indicate direct exposure to trans-nonachlor has a more potent pro-steatotic effect than exposure to DDE or oxychlordane. This pro-steatotic effect of trans-nonachlor appears to be predominately mediated via increased de novo lipogenesis and decreased fatty acid oxidation.

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“…Moreover, exposure to EDs may cause systemic alterations of the endocrine system, and not only affect the breast tissue. We believe that the serum POP-induced receptor activity is a good indicator for the long-term POP exposure, as serum levels of lipPOPs are highly correlated with the level in breast tissue (Rusiecki et al 2005, Artacho-Cordon et al 2015.…”

Section: Figurementioning

confidence: 98%

Receptor activities of persistent pollutant serum mixtures and breast cancer risk

Wielsøe¹,

Bjerregaard-Olesen²,

Kern³

et al. 2018

Endocrine-Related Cancer

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Studies on associations between persistent organic pollutants (POPs) and breast cancer risk are inconclusive. The majority of studies have evaluated the effect of single compounds, without considering multiple exposures to and interactions between different POPs. The present study aimed at evaluating breast cancer risk related to combined effects of serum POP mixtures on cellular receptor functions. Data on breast cancer cases ( = 77) and controls ( = 84) were collected among Greenlandic Inuit women. Serum mixtures of lipophilic POPs (lipPOPs), perfluoroalkyl acids (PFAAs) and dioxin-like POPs were extracted. The effect of the mixture extracts on the estrogen receptor (ER), androgen receptor (AR) and aryl hydrocarbon receptor (AhR) was determined using cell culture reporter gene assays. The serum mixtures were analyzed alone and upon co-exposure with natural receptor ligands to determine agonistic and antagonistic/competitive activity. We found that the frequency of lipPOP mixtures eliciting no, decreasing, or agonizing xenoandrogenic effect differed by breast cancer status. Using lipPOP mixtures with no effect on AR as reference, the mixtures with decreasing effects reduced breast cancer risk (OR: 0.30 (0.12; 0.76)). The AhR-toxic equivalent of serum mixtures was significantly lower in cases than in controls, and a reduced breast cancer risk was found when comparing the third tertile to the first (OR: 0.34 (0.14; 0.83)). We found no association between the xenoestrogenic activities of lipPOPs or PFAAs and breast cancer risk. Serum lipPOP mixtures are hormone disruptive and may influence breast cancer risk, whereas PFAAs seem to influence breast cancer risk through other pathways.

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Serum and adipose tissue as matrices for assessment of exposure to persistent organic pollutants in breast cancer patients

Cited by 57 publications

References 65 publications

Serum levels of environmental pollutants is a risk factor for breast cancer in Inuit: a case control study

Serum levels of environmental pollutants is a risk factor for breast cancer in Inuit: a case control study

Alterations in cellular lipid metabolism produce neutral lipid accumulation following exposure to the organochlorine compound trans‐nonachlor in rat primary hepatocytes

Receptor activities of persistent pollutant serum mixtures and breast cancer risk

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