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

Abstract

BACKGROUND: Most studies on endocrine-disrupting chemicals and breast cancer have focused on single compounds and have produced inconclusive findings. OBJECTIVES: We assessed the combined estrogenic effects of mixtures of xenoestrogens in serum and their relationship to breast cancer risk. METHODS: A total of 186 incident pretreatment breast cancer cases and 196 frequency-matched controls were randomly sampled from a large population-based multicase-control study in Spain. The total effective xenoestrogen burden attributable to organohalogenated xenoestrogens (TEXB-α) and endogenous hormones and more polar xenoestrogens (TEXB-β) was determined in serum samples using high-performance liquid chromatography and E-Screen bioassay. Odds ratios for breast cancer comparing tertiles of serum TEXB-α and TEXB-β were estimated using logistic models, and smooth risk trends were obtained using spline models. RESULTS: Cases had higher geometric mean TEXB-α and TEXB-β levels (8.32 and 9.94 Eeq pM/mL, respectively) than controls (2.99 and 5.96 Eeq pM/mL, respectively). The fully adjusted odds ratios for breast cancer (95% confidence intervals) comparing the second and third tertiles of TEXB-α with the first tertile were 1.77 (0.76, 4.10) and 3.45 (1.50, 7.97), respectively, and those for TEXB-β were 2.35 (1.10, 5.03) and 4.01 (1.88, 8.56), respectively. A steady increase in risk was evident across all detected TEXB-α levels and a sigmoidal trend was observed for TEXB-β. Individual xenoestrogens showed weak and opposing associations with breast cancer risk. CONCLUSIONS: This is the first study to show a strong positive association between serum total xenoestrogen burden and breast cancer risk, highlighting the importance of evaluating xenoestrogen mixtures, rather than single compounds, when studying hormone-related cancers. CITATION: Pastor-Barriuso R, Fernández MF, Castaño-Vinyals G, Whelan D, Pérez-Gómez B, Llorca J, Villanueva CM, Guevara M, Molina-Molina JM, Artacho-Cordón F, Barriuso-Lapresa L, Tusquets I, Dierssen-Sotos T, Aragonés N, Olea N, Kogevinas M, Pollán M. 2016. Total effective xenoestrogen burden in serum samples and risk for breast cancer in a population-based multicase-control study in Spain. Environ Health Perspect 124:1575-1582; http://dx.doi.org/10.1289/EHP157.