Serum Phthalate Concentrations and Biomarkers of Oxidative Stress in Adipose Tissue in a Spanish Adult Cohort.

The relationship between phthalates, a group of chemical pollutants classified as endocrine disruptors, and oxidative stress is not fully understood. The aim of the present hospital-based study was to explore the associations between circulating levels of 10 phthalate metabolites and 8 biomarkers of oxidative stress in adipose tissue. The study population (n = 143) was recruited in two hospitals in the province of Granada (Spain). Phthalate metabolite concentrations were analyzed by isotope diluted online-TurboFlow-LC-MS/MS in serum samples, while oxidative stress markers were measured by commercially available kits in adipose tissue collected during routine surgery. Statistical analyses were performed by MM estimators' robust linear regression and weighted quantile sum regression. Mainly, positive associations were observed of monomethyl phthalate (MMP), monoiso-butyl phthalate (MiBP), and mono-n-butyl phthalate (MnBP) (all low molecular weight phthalates) with glutathione peroxidase (GPx) and thiobarbituric acid reactive substances (TBARS), while an inverse association was found between monoiso-nonyl phthalate (MiNP) (high molecular weight phthalate) and the same biomarkers. WQS analyses showed significant effects of the phthalate mixture on GSH (ß = -30.089; p-value = 0.025) and GSSG levels (ß = -19.591; p-value = 0.030). Despite the limitations inherent to the cross-sectional design, our novel study underlines the potential influence of phthalate exposure on redox homeostasis, which warrants confirmation in further research.

Associations of circulating levels of phthalate metabolites with cytokines and acute phase reactants in a Spanish human cohort.

The associations between human phthalate exposure and the onset of chronic diseases with an immunological component (e.g., metabolic syndrome, cancer) remain unclear, partly due to the uncertainties in the underlying mechanisms. This study investigates cross-sectional associations of the concentrations of 10 phthalate metabolites with 19 cytokines and acute phase proteins in 213 serum samples of Spanish adults. The associations were explored by Spearman's correlation, multivariable linear regression, and weighted quantile sum regression analyses. In the multivariable analyses, levels of plasminogen activator inhibitor (PAI)-1 were positively associated with mono-n-butyl phthalate (fold-change per one IQR increase in phthalate levels, 95% Confidence Interval: 1.65, 1.45-1.88) and mono-iso-butyl phthalate (3.07, 2.39-3.95), mono-ethyl phthalate (2.05, 1.62-2.61), as well as categorized mono-iso-decyl and mono-benzyl phthalates. The same phthalates also were significantly associated with leptin, interleukin (IL)-18 and monocyte chemoattractant protein-1. Moreover, the proinflammatory markers IL-1ß, IL-17, IL-8, IL-6, IL-12, tumor necrosis factor, and lipopolysaccharide-binding protein showed positive and negative associations with, respectively, mono-(2-ethyl-hexyl) and mono-methyl phthalates. Finally, phthalate mixtures were positively associated with PAI-1, leptin, IL-18, IL-12, IL-8 and IL-1ß. Despite the cross-sectional design limitation, these associations point to relevant subclinical immuno-inflammatory actions of these pollutants, warranting confirmation in future studies.

Public healthcare costs associated with long-term exposure to mixtures of persistent organic pollutants in two areas of Southern Spain: A longitudinal analysis.

BACKGROUND: Polychlorinated biphenyls and organochlorine pesticides are persistent organic pollutants (POPs) that had been banned or restricted in many countries, including Spain. However, their ubiquity still poses environmental and human health threats. OBJECTIVE: To longitudinally explore public healthcare costs associated with long-term exposure to a mixture of 8 POPs in a cohort of residents of two areas of Granada Province, Southern Spain. METHODS: Longitudinal study in a subsample (n = 385) of GraMo adult cohort. Exposure assessment was performed by analyzing adipose tissue POP concentrations at recruitment. Average primary care (APC) and average hospital care (AHC) expenditures of each participant over 14 years were estimated using the data from their medical records. Data analyses were performed by robust MM regression, weighted quantile sum regression (WQS) and G-computation analysis. RESULTS: In the adjusted robust MM models for APC, most POPs showed positive beta coefficients, being Hexachlorobenzene (HCB) significantly associated (ß: 1.87; 95% Confidence interval (95%CI): 0.17, 3.57). The magnitude of this association increased (ß: 3.72; 95%CI: 0.80, 6.64) when the analyses were restricted to semi-rural residents, where ß-HCH was also marginally-significantly associated to APC (ß: 3.40; 95%CI: -0.10, 6.90). WQS revealed a positive but non-significant mixture association with APC (ß: 0.14; 95%CI: -0.06, 0.34), mainly accounted for by ß-HCH (54%) and HCB (43%), that was borderline-significant in the semi-rural residents (ß: 0.23; 95%CI: -0.01, 0.48). No significant results were observed in G-Computation analyses. CONCLUSION: Long-term exposure to POP mixtures might represent a modifiable factor increasing healthcare costs, thus affecting the efficiency of the healthcare systems. However, and owing the complexity of the potential causal pathways and the limitations of the present study, further research is warranted to fully elucidate ascertain whether interventions to reduce human exposure should be considered in healthcare policies.

Differential Bioaccumulation Patterns of α, ß-Hexachlorobenzene and Dicofol in Adipose Tissue from the GraMo Cohort (Southern Spain).

To identify bioaccumulation patterns of α-, ß- hexachlorocyclohexane (HCH) and dicofol in relation to sociodemographic, dietary, and lifestyle factors, adipose tissue samples of 387 subjects from GraMo cohort in Southern Spain were analyzed. Potential predictors of these organochlorine pesticides (OCP) levels were collected by face-to-face interviews and assessed by multivariable linear and logistic regression. OCPs were detected in 84.2% (ß-HCH), 21.7% (α-HCH), and 19.6% (dicofol) of the population. ß-HCH levels were positively related to age, body mass index (BMI), mother's occupation in agriculture during pregnancy, living in Poniente and Alpujarras, white fish, milk and water consumption, and negatively related to being male, living near to an agricultural area, working ≥10 years in agriculture, and beer consumption. Detectable α-HCH levels were positively related to age, BMI, milk consumption, mother's occupation in agriculture during pregnancy, and negatively with residence in Poniente and Alpujarras, Granada city, and Granada Metropolitan Area. Residence near to an agricultural area, smoking habit, white fish and water consumption, and living in Poniente and Alpujarras, Granada city and Granada Metropolitan Area were negatively associated with detectable dicofol levels. Our study revealed different bioaccumulation patterns of α, ß-HCH and dicofol, probably due to their dissimilar period of use, and emphasize the need for assessing the exposure to frequently overlooked pollutants.

Trace elements concentration in adipose tissue and the risk of incident type 2 diabetes in a prospective adult cohort.

The aim of this work was to study the associations of adipose tissue trace element concentrations with type 2 diabetes (T2DM) incidence over a 16-year follow-up period in an adult cohort from Southern Spain. 16-year T2DM incidence was gathered from hospital records. Chemical analyses of Cr, V, Zn, Fe, Cu and Se in adipose tissue were performed using inductively coupled plasma mass spectrometry. Multivariable Cox-regression models were used. Complementary cross-sectional analyses with markers of glucose homeostasis at recruitment were performed by multivariable linear regression. Out of 214 participants, 39 developed T2DM during the follow-up. Adipose tissue concentrations of Fe (HR = 1.97, 95% CI: 0.99 to 2.58, p = 0.057), Cr (HR = 1.58, 95% CI: 1.07-2.33, p = 0.022) and Cu (HR = 1.61, 95% CI: 1.01-2.58, p = 0.046) were individually associated with T2DM incidence. When Fe, Cr and Cu were simultaneously entered in a model, only Cr was significantly associated with T2DM incidence (HR = 1.68, 95% CI: 1.02-2.76, p = 0.041). Furthermore, adipose tissue V (ß = 0.283, p = 0.004) and Zn (ß = 0.217, p = 0.028) concentrations were positively associated with ß-pancreatic cell function (HOMA-ß), while Se showed an inverse association (ß = -0.049, p = 0.027). Although further research is warranted on the potential mechanisms of action, our results suggest that adipose tissue concentrations of certain trace elements (particularly Fe, Cr and Cu) are associated with the risk of incident T2DM, while V and Zn might have a protective effect. These biomarkers might complement prediction algorithms and contribute to identify patients with an increased risk of T2DM.

Associations of serum phthalate metabolites with thyroid hormones in GraMo cohort, Southern Spain.

The general population is continuously exposed to phthalates via various consumer products. Epidemiological research relating phthalate exposure to thyroid function during non-developmental periods is limited. This study aimed to investigate the associations between specific serum phthalate metabolites and indicators of thyroid function in adults. We measured 10 serum phthalate metabolites and thyroid hormones - total triiodothyronine (TT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) - in a subsample of 207 adults from the GraMo cohort. This subsample was made up of men and women (in equal proportions) of middle age (49 ± 17 years) and from Southern Spain (province of Granada). Data on age, sex, body mass index, residence area, tobacco use, alcohol consumption and attained education were obtained from a questionnaire. Phthalate metabolites were log-transformed and categorized into tertiles. Cross-sectional associations of each metabolite with thyroid hormones were analyzed using multivariable-adjusted linear regression models. The mixture effect of metabolite phthalates was assessed using weighted quantile sum regression. After multivariable-adjustment, the following phthalate metabolites were significantly associated with TT3 in a dose-response manner: MMP (ß = 0.90: 95% confidence interval 0.68,1.12), MEP (ß = 0.67: 0.44, 0.90), MiBP (ß = 0.49: 0.21, 0.77), MiDP (ß = 0.27: 0.03, 0.52), MBzP (ß = 0.51: 0.28, 0.73), MEHP (ß = -0.59: -0.82, -0.35) and MiNP (ß = -0.43: -0.71, -0.14), when comparing highest vs. lowest exposed. The sum of all metabolites was also linked to FT4 levels. No significant associations were observed for TSH except for MiNP. Although phthalate metabolites with different molecular weight showed opposite associations, overall metabolite concentrations seem to associate with increased TT3 and FT4 serum levels. The cross-sectional nature of this analysis limits causal inference.

Historical exposure to persistent organic pollutants and cardiovascular disease: A 15-year longitudinal analysis focused on pharmaceutical consumption in primary care.

BACKGROUND: Despite restrictions on their production and use, most of the population is still exposed to Persistent Organic Pollutants (POPs), including organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs). These chemicals are thought to contribute to the aetiology of highly prevalent chronic conditions, such as cardiovascular diseases (CVDs), although current evidences are still controversial. OBJECTIVES: To explore the potential contribution of historical POP exposure to 15-year pharmaceutical consumption in relation to CVD. METHODS: This study is framed within GraMo adult cohort. Participants (n = 387) were recruited in two hospitals in Granada province, Southern Spain (2003-2004). Historical exposure to 5 OCPs and 3 non-dioxine-like PCBs was estimated by analysing adipose tissue concentrations at recruitment. Pharmaceutical consumption from recruitment until year 2017 was quantified by reviewing dispensation databases. Average consumption increase (ACI) in CVD medication was calculated by subtracting average consumption in 2002 to the average yearly consumption during follow-up. ACI was expressed as Defined Daily Dose (DDD)/year units. Data analyses were carried out using a multivariable multinomial logistic regression and weighted quantile sum regression (WQS), with ACI categorized in quartiles (Q) as the dependent variable. RESULTS: Concentrations of most pollutants showed a positive trend with the quartiles of ACI. Particularly, PCB-153 showed increasing and statistically significant odds ratios (ORs) for Q2 (OR: 1.27, 95% confidence interval (CI): 1.07-1.52), Q3 (OR: 1.49, 95 %CI: 1.17-1.88) and Q4 (OR: 1.42, 95 %CI: 1.13-1.78) vs Q1. Similarly, beta-hexachlorocyclohexane (ß-HCH) also showed increasing ORs, that reached statistical significance in Q4 (OR: 1.36, 95 %CI: 1.06-1.74) vs Q1. These findings were corroborated by WQS analyses, that revealed a significant mixture effect, predominantly accounted for by PCB-153 and ß-HCH. DISCUSSION: Our results suggest that long-term POP exposure might represent a modifiable risk factor for CVD. These findings are relevant for public health campaigns and management, since pharmaceutical consumption is considered an indicator of both morbidity and health expenditure.

Adipose Tissue Redox Microenvironment as a Potential Link between Persistent Organic Pollutants and the 16-Year Incidence of Non-hormone-Dependent Cancer.

We aimed to assess the relationships among the adipose tissue's (AT) oxidative microenvironment, in situ accumulated persistent organic pollutant (POP) concentrations, and cancer development. POP and oxidative stress levels were quantified in AT samples from 382 adults recruited within the GraMo cohort (2003-2004) in Granada (Spain). The 16-year cancer incidence was ascertained by reviewing health/administrative databases. Cox-regression models and mediation analyses were performed. The enzymes superoxide dismutase (SOD) and glutathione reductase (GRd) were positively associated with the risk of non-hormone-dependent (NHD) cancer [adjusted hazard ratio (HR) 1.76; 95% confidence interval (CI): 1.17, 2.64 and HR 2.35; 95% CI: 1.41, 3.94, respectively]. After adjustment for covariates, polychlorinated biphenyl-138 (PCB-138) (HR 1.78; 95% CI: 1.03, 3.09), ß-hexachlorocyclohexane (ß-HCH) (HR 1.70; 95% CI: 1.09, 2.64), and hexachlorobenzene (HR 1.54; 95% CI: 1.02, 2.33) were also positively associated with the risk of NHD cancer. Although confidence intervals included the null value, probably because of the modest number of cancer cases, we observed a potential mediation effect of SOD and GRd on the associations between ß-HCH and the risk of NHD tumors (percent mediated = 33 and 47%, respectively). Our results highlight the relevance of human AT's oxidative microenvironment as a predictor of future cancer risk as well as its potential mediating role on POP-related carcinogenesis. Given their novelty, these findings should be interpreted with caution and confirmed in future studies.

Associations of accumulated selected persistent organic pollutants in adipose tissue with insulin sensitivity and risk of incident type-2 diabetes.

Continuous exposure to low doses of persistent organic pollutant (POPs), such as those occurring in the general population, might contribute to the burden of type 2 diabetes mellitus (T2DM). However, evidences from longitudinal studies are scarce. We aimed to explore the associations of accumulated POP exposure with the development of T2DM by means of 1) longitudinal associations with the 16-year incidence of the disease, and 2) complementary cross-sectional analyses with markers of glucose homeostasis at recruitment. Organochlorine pesticide and polychlorinated biphenyl (PCB) concentrations were analyzed in adipose tissue samples and incident T2DM cases were retrieved from clinical records. Homeostatic model assessment values of insulin sensitivity/resistance and ß-cell function at recruitment were calculated. Linear and Cox-regression models were performed. In individuals with normal weight/overweight (n = 293), we observed positive dose-response relationships between the studied POPs and T2DM risk, particularly for hexachlorobenzene (HCB) [hazard ratio (HR): 3.96 for 4th quartile versus 1st quartile (Q1); confidence interval (CI) 95%: 0.79, 19.71]. PCB-180 showed a positive but seemingly non-linear association with T2DM risk [HR of 3er quartile (Q3) versus Q1: 6.48; CI 95%: 0.82, 51.29]. Unadjustment for body mass index considerably increased the magnitude of the associations. In the cross-sectional study (n = 180), HCB and PCB-180 were inversely associated with insulin sensitivity and positively associated with insulin resistance parameters. Our results suggest that a higher burden of specific POPs in adipose tissue may disrupt glucose homeostasis, possibly contributing to increase T2DM risk, especially in non-obese adults.

Adipose tissue cadmium concentrations as a potential risk factor for insulin resistance and future type 2 diabetes mellitus in GraMo adult cohort.

Adipose tissue has been recently highlighted as a promising matrix for evaluation of cadmium's (Cd) long-term exposure although not frequently considered in epidemiological studies. The association between Cd exposure and type 2 Diabetes Mellitus (T2DM) remains unclear. This work aimed to explore the association between adipose tissue Cd levels and T2DM incidence over a 16-year follow-up in an adult cohort from Southern Spain considering smoking status. We also performed complementary cross-sectional analyses focused on subclinical markers of glucose homeostasis at recruitment. Clinical information was obtained from hospital databases. Socio-demographic characteristics, lifestyle and diet were collected by face-to-face interviews. Homeostatic model assessment (HOMA) values of insulin sensitivity/resistance and ß-cell function were calculated using fasting serum glucose, insulin, and C-peptide levels at recruitment. Adipose tissue Cd concentrations were quantified by inductively coupled plasma mass spectrometry. Statistical analyses were performed by means of Cox-regression and multivariable linear regression models. Participants in the 4th quartile (Q4) of Cd concentrations showed a non statistically-significant increased T2DM risk (Hazard Ratio (HR) Q4 vs Q1: 1.97; 95% Confidence Interval (CI): 0.69, 5.66). This association was particularly strong and suggestive in current smokers (HR: 2.19; 95% CI: 0.98, 4.98). Interestingly, smokers in the 2nd tertile (T2) of adipose tissue Cd levels showed increased log-transformed insulin resistance (beta T2 vs T1: 0.52; 95% CI: 0.07, 0.97), as well as higher log-transformed insulin levels (beta T2 vs T1: 0.52; 95% CI: 0.08, 0.95). We found evidences supporting that Cd exposure, particularly from tobacco smoking, could be a risk factor for T2DM. In addition, our results support the potential relevance of adipose tissue as a matrix for Cd exposure assessment.

Associations of residential and occupational history with the distribution of persistent pollutant mixtures in adipose tissue samples.

This research aims to explore clusters of a mixture of 15 Persistent Toxic Substances (PTSs) in the adipose tissue of 227 individuals of an adult cohort from Granada Province (Southern Spain). Information about residence and occupation during participants lifetime was gathered by means of validated questionnaires. Clusters of pollutants in the study population were identified by Principal Component Analyses (PCA). PCA analyses revealed three major clusters of pollutants: PC1, representing predominantly an assortment of metal(loid)s, namely aluminium, arsenic, chromium, nickel and lead; PC2, including mostly Organochlorine Pesticides (OCPs), such as HCB, ß-HCH and p,p'-DDE; and PC3, gathering mainly a mixture of Polychlorinated Biphenyls (PCB-138, PCB-153 and PCB-180) and metals (cadmium, cobalt and chromium). The patterns of distribution of individual pollutants and their mixtures were explored through Geographic Information Systems and multivariable linear regression models. Living in rural areas was associated with decreased levels of the mixture of PCBs and metals. Residents of industrial and heavy traffic areas showed increased levels of the mixture of metal(loid)s. Those living in rural and semi-rural areas at recruitment had decreased levels of the OCP mixture. Occupational history related to agriculture and food industry was associated with increased levels of the mixture of metal(loid)s, whereas those who had been involved in motor and industrial activities showed increased levels of the OCP mixture. Participants who had worked in cleaning and housekeeping activities for long periods showed decreased levels of the mixture of PCBs and metals. Our research revealed suggestive clusters of exposure, that emphasized the need for further epidemiological studies to address the effect of environmental pollutants from a mixture perspective. Results also highlight the potential of adipose tissue as a matrix for exposure assessment to combinations of different families of contaminants.

The efficacy of three-dimensional conformal radiation therapy on pain and quality of life in patients with painful bone metastases: a prospective study.

AIM: To evaluate the efficacy of radiation therapy in alleviating pain and improving the quality of life (QoL) with validated questionnaires in patients with painful bone metastases (BoM). METHODS: This prospective, observational study recruited 167 patients with painful BoM who were treated with palliative radiotherapy (PRT) from February 2015 to February 2018. After the first clinical assessment, the patients filled out specific questionnaires and underwent a fast radiotherapy treatment within 48 hours. The patients were followed up for eight weeks. RESULTS: The median age was 66.30 years. The most common primary cancer was lung cancer (31.1%). The most often prescribed scheme was 8 Gy in one fraction (70%). The patients experienced significant pain response and improved QoL compared with baseline, especially in the first two weeks after radiation. Overall, reduced pain and drug score were reported at two weeks of PRT in 68 (51.5%) and 37 (28%) of patients, respectively. CONCLUSIONS: PRT is an effective treatment option for patients with painful BoM.

Human biomonitoring as a tool for exposure assessment in industrially contaminated sites (ICSs). Lessons learned within the ICS and Health European Network.

BACKGROUND: the mixed and complex nature of industrially contaminated sites (ICSs) leads to heterogeneity in exposure and health risk of residents living nearby. Health, environment, and social aspects are strongly interconnected in ICSs, and local communities are often concerned about potential health impact and needs for remediation. The use of human biomonitoring (HBM) for impact assessment of environmental exposure is increasing in Europe. The COST Action IS1408 on Industrially Contaminated Sites and Health Network (ICSHNet) decided to reflect on the potential and limitations of HBM to assess exposure and early health effects associated with living near ICSs. OBJECTIVES: to discuss challenges and lessons learned for addressing environmental health impact near ICSs with HBM in order to identify needs and priorities for HBM guidelines in European ICSs. METHODS: based on the experience of the ICSHNet research team, six case studies from different European regions that applied HBM at ICSs were selected. The case studies were systematically compared distinguishing four phases: the preparatory phase; study design; study results; the impact of the results at scientific, societal, and political levels. RESULTS: all six case studies identified opportunities and challenges for applying HBM in ICS studies. A smart choice of (a combination of) sample matrices for biomarker analysis produced information about relevant time-windows of exposure which matched with the activities of the ICSs. Combining biomarkers of exposure with biomarkers of (early) biological effects, data from questionnaires or environmental data enabled fine-tuning of the results and allowed for more targeted remediating actions aimed to reduce exposure. Open and transparent communication of study results with contextual information and involvement of local stakeholders throughout the study helped to build confidence in the study results, gained support for remediating actions, and facilitated sharing of responsibilities. Using HBM in these ICS studies helped in setting priorities in policy actions and in further research. Limitations were the size of the study population, difficulties in recruiting vulnerable target populations, availability of validated biomarkers, and coping with exposure to mixtures of chemicals. CONCLUSIONS: based on the identified positive experiences and challenges, the paper concludes with formulating recommendations for a European protocol and guidance document for HBM in ICS. This could advance the use of HBM in local environmental health policy development and evaluation of exposure levels, and promote coordination and collaboration between researchers and risk managers.

A review of exposure assessment methods for epidemiological studies of health effects related to industrially contaminated sites.

BACKGROUND: this paper is based upon work from COST Action ICSHNet. Health risks related to living close to industrially contaminated sites (ICSs) are a public concern. Toxicology-based risk assessment of single contaminants is the main approach to assess health risks, but epidemiological studies which investigate the relationships between exposure and health directly in the affected population have contributed important evidence. Limitations in exposure assessment have substantially contributed to uncertainty about associations found in epidemiological studies. OBJECTIVES: to examine exposure assessment methods that have been used in epidemiological studies on ICSs and to provide recommendations for improved exposure assessment in epidemiological studies by comparing exposure assessment methods in epidemiological studies and risk assessments. METHODS: after defining the multi-media framework of exposure related to ICSs, we discussed selected multi-media models applied in Europe. We provided an overview of exposure assessment in 54 epidemiological studies from a systematic review of hazardous waste sites; a systematic review of 41 epidemiological studies on incinerators and 52 additional studies on ICSs and health identified for this review. RESULTS: we identified 10 multi-media models used in Europe primarily for risk assessment. Recent models incorporated estimation of internal biomarker levels. Predictions of the models differ particularly for the routes 'indoor air inhalation' and 'vegetable consumption'. Virtually all of the 54 hazardous waste studies used proximity indicators of exposure, based on municipality or zip code of residence (28 studies) or distance to a contaminated site (25 studies). One study used human biomonitoring. In virtually all epidemiological studies, actual land use was ignored. In the 52 additional studies on contaminated sites, proximity indicators were applied in 39 studies, air pollution dispersion modelling in 6 studies, and human biomonitoring in 9 studies. Exposure assessment in epidemiological studies on incinerators included indicators (presence of source in municipality and distance to the incinerator) and air dispersion modelling. Environmental multi-media modelling methods were not applied in any of the three groups of studies. CONCLUSIONS: recommendations for refined exposure assessment in epidemiological studies included the use of more sophisticated exposure metrics instead of simple proximity indicators where feasible, as distance from a source results in misclassification of exposure as it ignores key determinants of environmental fate and transport, source characteristics, land use, and human consumption behaviour. More validation studies using personal exposure or human biomonitoring are needed to assess misclassification of exposure. Exposure assessment should take more advantage of the detailed multi-media exposure assessment procedures developed for risk assessment. The use of indicators can be substantially improved by linking definition of zones of exposure to existing knowledge of extent of dispersion. Studies should incorporate more often land use and individual behaviour.

Risk of female breast cancer and serum concentrations of organochlorine pesticides and polychlorinated biphenyls: a case-control study in Tunisia.

The aim of this study was to investigate the association between serum concentrations of a group of organochlorine pesticides/polychlorinated biphenyls with xenoestrogenic potential and the risk of breast cancer in a female population from Tunisia. The relationship between serum levels of the pollutants and the risk of cancer was assessed using logistic regression analyses. In the unadjusted models, ß-hexachlorocyclohexane (ß-HCH), hexachlorobenzene, heptachlor, polychlorinated biphenyl congeners 138, 153, and 180, and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) were positively associated with breast cancer risk. However, when the models were further adjusted for the selected covariates, only ß-HCH and p,p'-DDE remained statistically significant, and heptachlor was borderline significant. In addition, analyses using POP concentration tertiles corroborated a positive dose-response relationship that was significant for p,p'-DDE (p-trend=0.020) and borderline significant for heptachlor (p-trend=0.078). A similar trend was also confirmed for ß-HCH, in which concentrations≥limit of detection were positively associated with breast cancer risk (vs. concentrations