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

Highlights

• We quantified persistent pollutant levels in serum and fat from cancer patients.

• We found positive correlations between fat and serum p,p′-DDE and HCB but not PCBs.

• We found certain differences in the predictors of serum and fat concentrations.

Abstract

The aim of this study was to assess differences between two biological matrices (serum and breast adipose tissue) in the evaluation of persistent organic pollutant (POP) exposure in breast cancer patients. The study population consisted of 103 women undergoing surgery for newly diagnosed breast carcinoma in a public hospital in Granada, Southern Spain. Independent variables were gathered from questionnaires and clinical records. POP concentrations were quantified in breast adipose tissue and serum samples. Spearman correlation tests were performed between pairs of POP concentrations and stepwise multivariable linear regression analyses were conducted to assess predictors of concentrations in the two matrices. p,p′- Dichlorodiphenyldichloroethylene (p,p′-DDE) showed the the highest median concentration in both matrices (194.34 and 173.84 ng/g lipid in adipose tissue and serum, respectively). Median wet-basis adipose tissue:serum ratios ranged from 109.34 to 651.62, while lipid-basis ratios ranged from 0.88 to 4.34. In general, we found significant positive correlation coefficients between pairs of POPs in adipose tissue and in serum, which were always higher in adipose tissue. We found positive and statistically significant correlations between serum and adipose tissue concentrations of p,p′-DDE and hexachlorobenzene (HCB) but not of polychlorinated biphenyls (PCBs). Age was positively associated with most POPs in adipose tissue and serum, while the body mass index was positively associated with adipose tissue HCB concentrations and negatively associated with serum PCB-153 and PCB-138 concentrations. Recent weight loss was inversely associated with POP residues in adipose tissue and positively associated with POP residues in serum. Serum HCB and PCB-180 concentrations were lower in patients who had received preoperative chemotherapy. According to our results, serum and adipose tissue POP concentrations in breast cancer patients may be differentially affected by external predictors. Taken together, these findings indicate the need to take account of the individual POP(s) under study and the biological matrix used when relating internal POP exposure to breast cancer disease and to make a careful selection of covariates for adjusting the model.

Introduction

Persistent organic pollutants (POPs) are a wide group of highly lipophilic environmental pollutants that tend to accumulate and biomagnify in the food chain, resulting in the considerable exposure of living organisms (UNEP, 2003). POPs include organochlorine pesticides (OCPs), such as dichlorodiphenyltrichloroethane (DDT) and its metabolites (notably, p,p′-dichlorodiphenyldichloroethylene [p,p′-DDE]), hexachlorobenzene (HCB), and polychlorinated biphenyls (PCBs), among others. While DDT and HCB were primarily commercialized for vector control and agricultural purposes, PCBs were mainly used as fluid insulators in electrical transformers and capacitors. Since the early 1970s, most countries have banned or severely restricted the production, handling, and disposal of most POPs. This is due to their high environmental persistence and their proven or suspected adverse human health effects at doses traditionally considered safe, including reproductive disorders, endocrine disruption, and carcinogenicity (Arrebola et al., 2013, Bonefeld-Jorgensen, 2010, Fernandez et al., 2007a, Fernandez et al., 2007b, Gasull et al., 2010, Krüger et al., 2012, Lee et al., 2014).

Despite their prohibition, POPs are still commonly detected in air, water and soil, among other environmental media (Syed et al., 2013). Besides respiratory and dermal routes, diet is believed to be the main route of exposure to POPs in the general population (Gasull et al., 2010). Due to their lipophilicity, POPs tend to bioaccumulate in fat components, and adipose tissue is therefore acknowledged to be the main deposit of these contaminants, accounting for all routes and sources of exposure and representing a stable and long-term reservoir of these compounds (Kohlmeier and Kohlmeier, 1995).

Hormone homeostasis is crucial in diseases related to the endocrine system, including the majority of breast cancers. Thus, estrogen signaling and the estrogen receptor (ER) have been implicated in breast cancer progression, and most human breast cancers start out as estrogen dependent (Saha Roy and Vadlamudi, 2011). In fact, ER-alpha antagonism is widely used in the treatment of ER-alpha-positive breast cancer patients. In this regard, some in vitro studies have revealed that exposure to some POPs can interact with ERs and cause estrogen-related effects, such as breast cancer cell proliferation. The suspected mechanisms of action have not been fully elucidated, but in vitro studies have shown that numerous POPs can interact with estrogen and/or androgen receptors, exerting significant effects at very low doses (Andersen et al., 2002, Bonefeld-Jørgensen et al., 2001, Grünfeld and Bonefeld-Jorgensen, 2004, Soto et al., 1994). In fact, the estrogenic potency of most POPs is approximately six orders of magnitude lower than of estradiol (Soto et al., 1994). Nevertheless, some epidemiological evidence has emerged on the potential role of POP exposure in the etiology of breast cancer, with a wide range of studies reporting positive associations (Aronson et al., 2000, Arrebola et al., 2015, Arrebola et al., 2014a, Boada et al., 2012, Bonefeld-Jorgensen et al., 2011, Bonefeld-Jørgensen et al., 2014, Ibarluzea et al., 2004), although others found no or even negative associations (Gatto et al., 2007, Itoh et al., 2009, Xu et al., 2010). Key differences among these studies include not only the study design and target population but also the biological matrix used to estimate the exposure, with serum and adipose tissue being the most frequent.

Whereas it is viable to obtain breast adipose tissue from patients undergoing surgery, the difficulties in obtaining these samples from other populations means that blood serum has more frequently been used as a matrix for exposure assessment of the general population. However, although many authors have found a high correlation between POP concentrations in serum and adipose tissue (López-Carrillo et al., 1999, Pauwels et al., 2000, Waliszewski et al., 2004, Whitcomb et al., 2005), it remains unclear whether serum POP concentrations can accurately reflect the body burden of these chemicals in all situations (Aronson et al., 2000, Arrebola et al., 2012a, Mussalo-Rauhamaa, 1991, Rusiecki et al., 2005, Wolff et al., 2000). In fact, it is possible that POP concentrations in the two matrices may be strongly correlated in some cases but not in others, given that serum concentrations are influenced not only by current exposure but also by the recirculation of POPs from adipose tissue due to lipolysis (Crinnion, 2009).

The steady-state partitioning of POPs between serum and breast adipose tissue is an important consideration in attempts to predict adipose tissue concentrations from those found in serum (Rusiecki et al., 2005). Thus, it has been suggested that variations in the lipid content of serum can induce changes in the partitioning coefficient between adipose tissue and serum POP concentrations (Guo et al., 1987). In this regard, most chemotherapy (QT) treatments are believed to reduce concentrations of serum lipid fractions [e.g. triglycerides, total cholesterol and low density lipoprotein (LDL)] in patients with breast cancer (Ray et al., 2001, Shah et al., 2008). It is therefore of interest to assess whether the serum POP concentrations of these patients can always predict the total body burden. Furthermore, given the widespread application of neoadjuvant treatments in breast cancer, it is relevant to assess whether they can act as confounders or effect modifiers in the potential association between POPs and breast cancer risk.

The aim of this study was to assess differences between two biological matrices (serum and breast adipose tissue) in the evaluation of POP exposure in breast cancer patients.