title: Dioxin exposure and cancer risk in the Seveso Women's Health Study.
abstract: BACKGROUND
  2,3,7,8-Tetrachlorodibenzo-para-dioxin (TCDD), a widespread environmental contaminant, disrupts multiple endocrine pathways. The International Agency for Research on Cancer classified TCDD as a known human carcinogen, based on predominantly male occupational studies of increased mortality from all cancers combined.
  
  
  OBJECTIVE
  After a chemical explosion on 10 July 1976 in Seveso, Italy, residents experienced some of the highest levels of TCDD exposure in a human population. In 1996, we initiated the Seveso Women's Health Study (SWHS), a retrospective cohort study of the reproductive health of the women. We previously reported a significant increased risk for breast cancer and a nonsignificant increased risk for all cancers combined with individual serum TCDD, but the cohort averaged only 40 years of age in 1996. Herein we report results for risk of cancer from a subsequent follow-up of the cohort in 2008.
  
  
  METHODS
  In 1996, we enrolled 981 women who were 0-40 years of age in 1976, lived in the most contaminated areas, and had archived sera collected near the explosion. Individual TCDD concentration was measured in archived serum by high-resolution mass spectrometry. A total of 833 women participated in the 2008 follow-up study. We examined the relation of serum TCDD with cancer incidence using Cox proportional hazards models.
  
  
  RESULTS
  In total, 66 (6.7%) women had been diagnosed with cancer. The adjusted hazard ratio (HR) associated with a 10-fold increase in serum TCDD for all cancers combined was significantly increased [adjusted HR = 1.80; 95% confidence interval (CI): 1.29, 2.52]. For breast cancer, the HR was increased, but not significantly (adjusted HR = 1.44; 95% CI: 0.89, 2.33).
  
  
  CONCLUSIONS
  Individual serum TCDD is significantly positively related with all cancer incidence in the SWHS cohort, more than 30 years later. This all-female study adds to the epidemiologic evidence that TCDD is a multisite carcinogen.
authors.affiliation: Center for Environmental Research and Children's Health, School of Public Health, University of California at Berkeley, Berkeley, California 94720, USA. mwarner@berkeley.edu
authors.forename: Marcella
authors.initials: M
authors.lastname: Warner
authors.forename: Paolo
authors.initials: P
authors.lastname: Mocarelli
authors.forename: Steven
authors.initials: S
authors.lastname: Samuels
authors.forename: Larry
authors.initials: L
authors.lastname: Needham
authors.forename: Paolo
authors.initials: P
authors.lastname: Brambilla
authors.forename: Brenda
authors.initials: B
authors.lastname: Eskenazi
mesh_terms: D015331:Cohort Studies; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D013058:Mass Spectrometry; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology*; D000072317:Polychlorinated Dibenzodioxins / Q000097:blood / Q000633:toxicity*; D016016:Proportional Hazards Models; D012189:Retrospective Studies
chemical_list: D000072317:Polychlorinated Dibenzodioxins