Serum Dioxin Concentrations and Breast Cancer Risk in the Seveso Women's Health Study. (Research Articles)
Warner, Marcella, Eskenazi, Brenda, Mocarelli, Paolo, Gerthoux, Pier Mario, Samuels, Steven, Needham, Larry, Patterson, Donald, Brambilla, Paolo, Environmental Health Perspectives
2,3,7,8-Tetrachlorodibenzo-p-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.sub.10] 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. Key words: breast neoplasms, dioxin, epidemiology, tetrachlorodibenzo-p-dioxin.
The compound 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin) is the most toxic member of a class of planar, halogenated aromatic hydrocarbons (1,2). TCDD is a widespread environmental contaminant produced by various chemical reactions and combustion processes (3). It is highly lipophilic and extremely stable and thus accumulates in the food chain (2). TCDD has a half-life of 7-9 years in humans (4). In animals, TCDD is a potent carcinogen and has been shown to disrupt multiple endocrine pathways (1,2,5). The International Agency for Research on Cancer has classified TCDD as a known human carcinogen, primarily on the basis of occupational studies of increased mortality from all cancers combined, but no particular cancer sites were predominant (5).
The few epidemiologic studies that have examined the relationship between TCDD exposure and breast cancer risk are limited by small sample size and lack of individual exposure data. Breast cancer mortality (6,7) and incidence (8) increased in female workers employed in the production of TCDD-contaminated phenoxyherbicides. Significantly increased mortality from breast cancer was reported in a Russian town with a chemical plant known to be a source of TCDD (9). However, a hospital-based breast cancer case-control study found no difference in breast tissue concentration of TCDD between women with breast cancer and women with benign breast disease, but the level of exposure was low (1.0-7.9 ppt, lipid-adjusted) (10).
On 10 July 1976, an explosion at a trichlorophenol manufacturing plant near Seveso, Italy, resulted in the highest TCDD levels known in human residential populations (11). Up to 30 kg of TCDD were deposited over the surrounding area (~18 [km.sup.2]) (12), which was divided into exposure zones (A, B, R, non-ABR) based on TCDD measurements in soil. Ten- and 15-year follow-up studies of the Seveso population found no increased risk for breast cancer incidence (13,14) or mortality (15-17). However, after 20 years of follow-up, a statistically nonsignificant increased risk for breast cancer mortality emerged among women who resided in zones A or B, the most heavily contaminated areas, and who were younger than 55 years at death [relative risk (RR) = 1. …