Abstract
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.
Full Text
The Full Text of this article is available as a PDF (511.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Akins J. R., Waldrep K., Bernert J. T., Jr The estimation of total serum lipids by a completely enzymatic 'summation' method. Clin Chim Acta. 1989 Oct 16;184(3):219–226. doi: 10.1016/0009-8981(89)90054-5. [DOI] [PubMed] [Google Scholar]
- Bertazzi A., Pesatori A. C., Consonni D., Tironi A., Landi M. T., Zocchetti C. Cancer incidence in a population accidentally exposed to 2,3,7,8-tetrachlorodibenzo-para-dioxin. Epidemiology. 1993 Sep;4(5):398–406. doi: 10.1097/00001648-199309000-00004. [DOI] [PubMed] [Google Scholar]
- Bertazzi P. A., Zocchetti C., Guercilena S., Consonni D., Tironi A., Landi M. T., Pesatori A. C. Dioxin exposure and cancer risk: a 15-year mortality study after the "Seveso accident". Epidemiology. 1997 Nov;8(6):646–652. [PubMed] [Google Scholar]
- Bertazzi P. A., Zocchetti C., Pesatori A. C., Guercilena S., Consonni D., Tironi A., Landi M. T. Mortality of a young population after accidental exposure to 2,3,7,8-tetrachlorodibenzodioxin. Int J Epidemiol. 1992 Feb;21(1):118–123. doi: 10.1093/ije/21.1.118. [DOI] [PubMed] [Google Scholar]
- Bertazzi P. A., Zocchetti C., Pesatori A. C., Guercilena S., Sanarico M., Radice L. Ten-year mortality study of the population involved in the Seveso incident in 1976. Am J Epidemiol. 1989 Jun;129(6):1187–1200. doi: 10.1093/oxfordjournals.aje.a115240. [DOI] [PubMed] [Google Scholar]
- Birnbaum L. S. Developmental effects of dioxins and related endocrine disrupting chemicals. Toxicol Lett. 1995 Dec;82-83:743–750. doi: 10.1016/0378-4274(95)03592-3. [DOI] [PubMed] [Google Scholar]
- Birnbaum L. S. The mechanism of dioxin toxicity: relationship to risk assessment. Environ Health Perspect. 1994 Nov;102 (Suppl 9):157–167. doi: 10.1289/ehp.94102s9157. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brown N. M., Lamartiniere C. A. Xenoestrogens alter mammary gland differentiation and cell proliferation in the rat. Environ Health Perspect. 1995 Jul-Aug;103(7-8):708–713. doi: 10.1289/ehp.95103708. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brown N. M., Manzolillo P. A., Zhang J. X., Wang J., Lamartiniere C. A. Prenatal TCDD and predisposition to mammary cancer in the rat. Carcinogenesis. 1998 Sep;19(9):1623–1629. doi: 10.1093/carcin/19.9.1623. [DOI] [PubMed] [Google Scholar]
- Eskenazi B., Mocarelli P., Warner M., Samuels S., Needham L., Patterson D., Brambilla P., Gerthoux P. M., Turner W., Casalini S. Seveso Women's Health Study: does zone of residence predict individual TCDD exposure? Chemosphere. 2001 May-Jun;43(4-7):937–942. doi: 10.1016/s0045-6535(00)00454-9. [DOI] [PubMed] [Google Scholar]
- Eskenazi B., Mocarelli P., Warner M., Samuels S., Vercellini P., Olive D., Needham L., Patterson D., Brambilla P. Seveso Women's Health Study: a study of the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on reproductive health. Chemosphere. 2000 May-Jun;40(9-11):1247–1253. doi: 10.1016/s0045-6535(99)00376-8. [DOI] [PubMed] [Google Scholar]
- Gierthy J. F., Bennett J. A., Bradley L. M., Cutler D. S. Correlation of in vitro and in vivo growth suppression of MCF-7 human breast cancer by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Cancer Res. 1993 Jul 1;53(13):3149–3153. [PubMed] [Google Scholar]
- Hardell L., Lindström G., Liljegren G., Dahl P., Magnuson A. Increased concentrations of octachlorodibenzo-p-dioxin in cases with breast cancer--results from a case-control study. Eur J Cancer Prev. 1996 Oct;5(5):351–357. doi: 10.1097/00008469-199610000-00007. [DOI] [PubMed] [Google Scholar]
- Holcomb M., Safe S. Inhibition of 7,12-dimethylbenzanthracene-induced rat mammary tumor growth by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Cancer Lett. 1994 Jul 15;82(1):43–47. doi: 10.1016/0304-3835(94)90144-9. [DOI] [PubMed] [Google Scholar]
- Kelsey J. L. Breast cancer epidemiology: summary and future directions. Epidemiol Rev. 1993;15(1):256–263. doi: 10.1093/oxfordjournals.epirev.a036112. [DOI] [PubMed] [Google Scholar]
- Kogevinas M., Becher H., Benn T., Bertazzi P. A., Boffetta P., Bueno-de-Mesquita H. B., Coggon D., Colin D., Flesch-Janys D., Fingerhut M. Cancer mortality in workers exposed to phenoxy herbicides, chlorophenols, and dioxins. An expanded and updated international cohort study. Am J Epidemiol. 1997 Jun 15;145(12):1061–1075. doi: 10.1093/oxfordjournals.aje.a009069. [DOI] [PubMed] [Google Scholar]
- Kreuzer P. E., Csanády G. A., Baur C., Kessler W., Päpke O., Greim H., Filser J. G. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and congeners in infants. A toxicokinetic model of human lifetime body burden by TCDD with special emphasis on its uptake by nutrition. Arch Toxicol. 1997;71(6):383–400. doi: 10.1007/s002040050402. [DOI] [PubMed] [Google Scholar]
- Lewis B. C., Hudgins S., Lewis A., Schorr K., Sommer R., Peterson R. E., Flaws J. A., Furth P. A. In utero and lactational treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin impairs mammary gland differentiation but does not block the response to exogenous estrogen in the postpubertal female rat. Toxicol Sci. 2001 Jul;62(1):46–53. doi: 10.1093/toxsci/62.1.46. [DOI] [PubMed] [Google Scholar]
- Lipworth L. Epidemiology of breast cancer. Eur J Cancer Prev. 1995 Feb;4(1):7–30. doi: 10.1097/00008469-199502000-00002. [DOI] [PubMed] [Google Scholar]
- Manz A., Berger J., Dwyer J. H., Flesch-Janys D., Nagel S., Waltsgott H. Cancer mortality among workers in chemical plant contaminated with dioxin. Lancet. 1991 Oct 19;338(8773):959–964. doi: 10.1016/0140-6736(91)91835-i. [DOI] [PubMed] [Google Scholar]
- Mocarelli P., Brambilla P., Gerthoux P. M., Patterson D. G., Jr, Needham L. L. Change in sex ratio with exposure to dioxin. Lancet. 1996 Aug 10;348(9024):409–409. doi: 10.1016/s0140-6736(05)65030-1. [DOI] [PubMed] [Google Scholar]
- Mocarelli P., Gerthoux P. M., Ferrari E., Patterson D. G., Jr, Kieszak S. M., Brambilla P., Vincoli N., Signorini S., Tramacere P., Carreri V. Paternal concentrations of dioxin and sex ratio of offspring. Lancet. 2000 May 27;355(9218):1858–1863. doi: 10.1016/S0140-6736(00)02290-X. [DOI] [PubMed] [Google Scholar]
- Needham L. L., Gerthoux P. M., Patterson D. G., Jr, Brambilla P., Turner W. E., Beretta C., Pirkle J. L., Colombo L., Sampson E. J., Tramacere P. L. Serum dioxin levels in Seveso, Italy, population in 1976. Teratog Carcinog Mutagen. 1997;17(4-5):225–240. [PubMed] [Google Scholar]
- Patterson D. G., Jr, Hampton L., Lapeza C. R., Jr, Belser W. T., Green V., Alexander L., Needham L. L. High-resolution gas chromatographic/high-resolution mass spectrometric analysis of human serum on a whole-weight and lipid basis for 2,3,7,8-tetrachlorodibenzo-p-dioxin. Anal Chem. 1987 Aug 1;59(15):2000–2005. doi: 10.1021/ac00142a023. [DOI] [PubMed] [Google Scholar]
- Pesatori A. C., Consonni D., Tironi A., Zocchetti C., Fini A., Bertazzi P. A. Cancer in a young population in a dioxin-contaminated area. Int J Epidemiol. 1993 Dec;22(6):1010–1013. doi: 10.1093/ije/22.6.1010. [DOI] [PubMed] [Google Scholar]
- Pirkle J. L., Wolfe W. H., Patterson D. G., Needham L. L., Michalek J. E., Miner J. C., Peterson M. R., Phillips D. L. Estimates of the half-life of 2,3,7,8-tetrachlorodibenzo-p-dioxin in Vietnam Veterans of Operation Ranch Hand. J Toxicol Environ Health. 1989;27(2):165–171. doi: 10.1080/15287398909531288. [DOI] [PubMed] [Google Scholar]
- Reed P. I., Jazrawi R. P., Northfield T. C., Carr-Locke D., Mountford R. A., Williams J. G., Schiller K. F., English J. R. Enprostil, a prostaglandin E2 analogue, in the treatment of gastric ulcer--a multicentre comparison with pirenzepine. Br J Clin Pract. 1990 Feb;44(2):48–51. [PubMed] [Google Scholar]
- Revich B., Aksel E., Ushakova T., Ivanova I., Zhuchenko N., Klyuev N., Brodsky B., Sotskov Y. Dioxin exposure and public health in Chapaevsk, Russia. Chemosphere. 2001 May-Jun;43(4-7):951–966. doi: 10.1016/s0045-6535(00)00456-2. [DOI] [PubMed] [Google Scholar]
- Safe S., Wang F., Porter W., Duan R., McDougal A. Ah receptor agonists as endocrine disruptors: antiestrogenic activity and mechanisms. Toxicol Lett. 1998 Dec 28;102-103:343–347. doi: 10.1016/s0378-4274(98)00331-2. [DOI] [PubMed] [Google Scholar]
- di Domenico A., Silano V., Viviano G., Zapponi G. Accidental release of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at Sèveso, Italy. V. Environmental persistence of TCDD in soil. Ecotoxicol Environ Saf. 1980 Sep;4(3):339–345. doi: 10.1016/0147-6513(80)90035-4. [DOI] [PubMed] [Google Scholar]
