title: 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.
  
  
  OBJECTIVE
  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.
  
  
  BACKGROUND
  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.
authors.affiliation: Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pastor-Barriuso
authors.forename: Mariana F
authors.initials: MF
authors.lastname: Fernández
authors.forename: Gemma
authors.initials: G
authors.lastname: Castaño-Vinyals
authors.forename: Denis
authors.initials: D
authors.lastname: Whelan
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pérez-Gómez
authors.forename: Javier
authors.initials: J
authors.lastname: Llorca
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Villanueva
authors.forename: Marcela
authors.initials: M
authors.lastname: Guevara
authors.forename: José-Manuel
authors.initials: JM
authors.lastname: Molina-Molina
authors.forename: Francisco
authors.initials: F
authors.lastname: Artacho-Cordón
authors.forename: Laura
authors.initials: L
authors.lastname: Barriuso-Lapresa
authors.forename: Ignasi
authors.initials: I
authors.lastname: Tusquets
authors.forename: Trinidad
authors.initials: T
authors.lastname: Dierssen-Sotos
authors.forename: Nuria
authors.initials: N
authors.lastname: Aragonés
authors.forename: Nicolás
authors.initials: N
authors.lastname: Olea
authors.forename: Manolis
authors.initials: M
authors.lastname: Kogevinas
authors.forename: Marina
authors.initials: M
authors.lastname: Pollán