Evidence From Humans
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Serum dioxin concentrations and breast cancer risk in the Seveso Women's Health Study
Warner, M., Eskenazi, B., Mocarelli, P., Gerthoux, P. M., Samuels, S., Needham, L., Patterson, D., Brambilla, P. Environ Health Perspect. 2002. 110:7, 625-8.
Topic area
Environmental pollutant - Dioxin (TCDD)
Funding agency
NIEHS Other: NIH, EPA, Endometriosis Association,
Study Participants
Menopausal Status
The menopausal status of women included in this study is listed here.
Pre menopausal
Post menopausal
Number in Cohort
Cohort: 981
Cohort participation rate
Greater than 70%
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
Participants of the Seveso Women's Health Study: Women who were infants to 40 years old in 1976 and resided at that time in the zones most highly contaminated (A or B) with TCDD in an industrial accident in Seveso, Italy, and had adequate stored sera collected soon after the explosion
Exposures investigated
Dioxin (TCDD) concentration in the first serum sample collected between 1976 and 1981, lipid-weight basis in parts per trillion. Concentrations from later samples were back-extrapolated to 1977.
Early life exposures considered
Some cases were exposed as teenagers.
Statistical Analysis
Breast cancer outcome investigated
Other: Age at breast cancer diagnosis
Ethnic groups with separate analysis
If this study provided a separate analysis by ethnic or racial group, the groups are listed here.
Confounders considered
Other breast cancer risk factors, such as family history, age at first birth, and hormone replacement therapy use, that were taken into account in the study.
Gravidity, parity, age at first pregnancy, age at last pregnancy, lactation, family history of breast cancer, age at menarche, current body mass index, oral contraceptive use, menarcheal status at explosion, menopause status at diagnosis, weight, height,
Genetic characterization included
If the study analyzed relationships between environmental factors and inherited genetic variations, this field will be marked “Yes.” “No”, if not.
Description of major analysis
Cox proportional hazard modeling. Subjects enter analysis at age at time of the explosion.
Strength of associations reported
TCDD as a continuous variable: Hazard Ratio = 2.1 (95% CI, 1.0-4.6) ("That is, for a 10-fold increase in TCDD..., a doubling of the hazard rate is predicted." p. 627) Test for trend p = 0.05. No single variable found to confound.
When TCDD is considered as a categorical variable, risk is elevated in the top two exposure groups, but confidence intervals include one.
Results Comments
Average age at interview is 40.8 years, which is young for breast cancer diagnosis. In addition, the youngest women in the cohort were more highly exposed. This study differs from results of earlier follow-up through 1986.
2,3,7,8-Tetrachlorodibenzo-(italic)p(/italic)-dioxin (TCDD or dioxin), a widespread environmental contaminant, has been shown to disrupt multiple endocrine pathways. The International Agency for Research on Cancer classified TCDD as a known human carcinogen, primarily based on occupational studies of increased mortality from all cancers combined. Using data from the Seveso Women's Health Study (SWHS), we examined the association between individual serum TCDD levels and breast cancer risk in women residing around Seveso, Italy, in 1976, at the time of an industrial explosion that resulted in the highest known population exposure to TCDD. The SWHS cohort comprises 981 women who were infants to 40 years old in 1976, resided in the most contaminated areas at the time of the explosion, and had archived sera that was collected soon after the explosion. For each woman, serum TCDD exposure was measured by high-resolution mass spectrometry. Cancer cases were identified during interview and confirmed by medical record. At interview, 15 women (1.5%) had been diagnosed with breast cancer and serum TCDD levels for cases ranged from 13 to 1,960 ppt. Cox proportional hazards modeling showed that the hazard ratio for breast cancer associated with a 10-fold increase in serum TCDD levels (log(subscript)10(/subscript) TCDD) was significantly increased to 2.1 (95% confidence interval, 1.0-4.6). Covariate-adjusted results were not different. Individual serum TCDD is significantly related with breast cancer incidence among women in the SWHS cohort. Continued follow-up of the cohort will help shed light on the possible role of TCDD in the pathogenesis of breast cancer.
Author address
School of Public Health, University of California at Berkeley, Berkeley, California 94720, USA. mwarner@uclinik4.berkeley.edu
Reviewers Comments
Animal and cell evidence supports multiple mechanistic explanations, including effects on mammary gland development.
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