Academic journal article Environmental Health Perspectives

Total Effective Xenoestrogen Burden in Serum Samples and Risk for Breast Cancer in a Population-Based Multicase-Control Study in Spain

Academic journal article Environmental Health Perspectives

Total Effective Xenoestrogen Burden in Serum Samples and Risk for Breast Cancer in a Population-Based Multicase-Control Study in Spain

Article excerpt


Malignant breast tumors are the leading cause of cancer in women worldwide in terms of incidence and mortality (Ferlay et al. 2013). Despite efforts to elucidate breast cancer etiology, genetic determinants and well-established risk factors explain a limited amount of the global burden of this disease (Barnes et al. 2011; Howell et al. 2014; Sprague et al. 2008). It is noteworthy that most recognized determinants of breast cancer, such as reproductive history, alcohol intake, obesity, and use of hormone therapy, exert their effects, at least in part, by modifying the time and intensity of the exposure of the mammary gland to steroidal hormones (Brown and Hankinson 2015; HilakiviClarke et al. 2013; MacMahon 2006; Renehan et al. 2015; Seitz et al. 2012).

Laboratory studies, specifically rodent models, support the implication of environmental pollutants in breast cancer development (Dhimolea et al. 2014; Rudel et al. 2007). Endocrine-disrupting chemicals (EDCs) are among the 17 chemical groups prioritized for evaluation in epidemiological studies of breast cancer (Rudel et al. 2014) because of their potential to act as xenoestrogens or to modulate estrogenic activity via different pathways [Gibson and Saunders 2014; World Health Organization/ United Nations Environment Programme (WHO/UNEP) 2013]. Hundreds of EDCs are present in human breast tissue, but epidemiological evidence linking these substances with breast cancer is inconclusive (WHO/UNEP 2013). Most previous studies have focused on individual EDCs with weak estrogenic effects, thus failing to consider multiple exposures and interactions involving different EDCs and physiological hormones (Fernandez et al. 2014). Functional tests measuring the combined estrogenic activity of mixtures of EDCs offer a promising approach for an aggregated exposure assessment. A case-control study reported a positive association between the combined effect of environmental estrogens in human adipose tissue and breast cancer risk (Ibarluzea et al. 2004). However, adipose tissue is difficult to obtain in population-based studies, and it would be of great practical value to assess the estrogenic potential of EDC mixtures present in blood samples (Rudel et al. 2014).

In the present study, we measured the combined estrogenic activity of mixtures of xenoestrogens in serum samples and evaluated its relationship to breast cancer risk in a subsample of cases and controls from a large population-based multicase-control study in Spain (MCC-Spain).


Study Population

MCC-Spain ( is a population-based multicase-control study conducted between 2008 and 2013 in 12 Spanish provinces to identify environmental, personal, and genetic factors related to five common cancers: breast, prostate, colorectal, stomach, and chronic lymphocytic leukemia. The study design has been previously reported (Castano-Vinyals et al. 2015). Briefly, the study recruited 6,082 patients 20-85 years old with histologically confirmed incident cancer, including 1,750 breast cancers, 1,115 prostate cancers, 2,171 colorectal cancers, 492 gastroesophageal cancers, and 554 cases of leukemia, as well as a single set of 4,101 population controls. The response rates were 69% among breast cancer cases and 54% among female controls. All participants completed computer-assisted personal interviews on sociodemographic factors, self-reported anthropometric data, lifestyle, reproductive history, hormonal factors, medications, and personal and family medical history. Blood samples were collected from 76% of participants. The study was approved by the ethics committees of the participating institutions. Written informed consent was obtained from each participant.

For this analysis, we randomly selected 204 breast cancer cases from among those who agreed to donate blood samples in the provinces of Madrid, Barcelona, Navarra, and Cantabria; we also selected 204 female controls who were frequency-matched to cases by province, 5-year age interval, and 2-unit category of body mass index. …

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