Cancer Causes & Control

, Volume 16, Issue 5, pp 525–535 | Cite as

Adipose levels of dioxins and risk of breast cancer

  • Peggy Reynolds
  • Susan E. Hurley
  • Myrto Petreas
  • Debbie E. Goldberg
  • Daniel Smith
  • Debra Gilliss
  • M. Ellen. Mahoney
  • Stefanie S. Jeffrey


Objective: Our objective was to evaluate the breast cancer risk associated with body burden levels of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs).

Methods: We conducted a hospital-based case-control study among 79 women diagnosed with invasive breast cancer and 52 controls diagnosed with benign breast conditions. We collected breast adipose tissue and analyzed it for all 17 2,3,7,8-substitituted PCDD/PCDFs. We used unconditional logistic regression to calculate age- and race-adjusted exposure-specific odds ratios (ORs) and 95% confidence intervals (CI) for each individual PCDD/PCDF congener as well as for the summary measures (I-TEQ, Adj-TEQ).

Results: Dioxin levels were consistent with reports from other small, contemporary studies of body burdens in the U.S. None of the odds ratios for any of the congeners or summary measures differed significantly from one. Especially for the PCDF congeners, point estimates tended to be below one. One notable exception was octachlorodibenzo-p-dioxin (OCDD), for which the odds ratio for the second and third tertiles appeared modestly elevated (OR = 1.22, 95% CI: 0.47:3.16 and OR = 1.62, 95% CI: 0.64:4.12, respectively), though the test for trend was not significant (p = 0.36).

Conclusion: Breast cancer risk was not associated with adipose levels of PCDD/PCDFs. More study is suggested among women of color who may have higher body burden levels of these compounds.


breast neoplasms adipose tissue body burden dioxins case-control studies 























Adjusted Toxic Equivalents (congeners below detection are omitted)




degrees celsius


confidence interval


California Department of Toxic Substances Control


detection limit


Hazardous Materials Laboratory


International Agency for Research on Cancer


International Toxic Equivalents






sodium sulfate


odds ratio


polybrominated diphenyl ethers


polychlorinated biphenyls


polychlorinated dibenzo-p-dioxins


polychlorinated dibenzofurans


picograms per gram – 10−12


standardized mortality ratio


Seveso Women’s Health Study


Toxic Equivalents


United States






Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Madigan, MP, Ziegler, RG, Benichou, J, Byrne, C, Hoover, RN 1995Proportion of breast cancer cases in the United States explained by well-established risk factorsJ Natl Cancer Inst8716811685PubMedGoogle Scholar
  2. 2.
    Aronson, KJ, Miller, AB, Woolcott, CG.,  et al. 2000Breast adipose tissue concentrations of polychlorinated biphenyls and other organochlorines and breast cancer riskCancer Epidemiol Biomarkers Prev95563PubMedGoogle Scholar
  3. 3.
    Bagga, D, Anders, KH, Wang, HJ, Roberts, E, Glaspy, JA 2000Organochlorine pesticide content of breast adipose tissue from women with breast cancer and control subjectsJ Natl Cancer Inst92750753PubMedGoogle Scholar
  4. 4.
    Dello Iacovo, R, Celentano, E, Strollo, AM, Iazzetta, G, Capasso, I, Randazzo, G 1999Organochlorines and breast cancer. A study on Neapolitan womenAdv Exp Med Biol4725766PubMedGoogle Scholar
  5. 5.
    Dewailly, E, Dodin, S, Verreault, R.,  et al. 1994High organochlorine body burden in women with estrogen receptor-positive breast cancerJ Natl Cancer Inst86232234PubMedGoogle Scholar
  6. 6.
    Dorgan, JF, Brock, JW, Rothman, N.,  et al. 1999Serum organochlorine pesticides and PCBs and breast cancer risk: results from a prospective analysis (USA)Cancer Causes Control10111PubMedGoogle Scholar
  7. 7.
    Guttes, S, Failing, K, Neumann, K, Kleinstein, J, Georgii, S, Brunn, H 1998Chlororganic pesticides and polychlorinated biphenyls in breast tissue of women with benign and malignant breast diseaseArch Environ Contam Toxicol35140147PubMedGoogle Scholar
  8. 8.
    Helzlsouer, KJ, Alberg, AJ, Huang, HY.,  et al. 1999Serum concentrations of organochlorine compounds and the subsequent development of breast cancerCancer Epidemiol Biomarkers Prev8525532PubMedGoogle Scholar
  9. 9.
    Hoyer, AP, Grandjean, P, Jorgensen, T, Brock, JW, Hartvig, HB 1998Organochlorine exposure and risk of breast cancerLancet35218161820CrossRefPubMedGoogle Scholar
  10. 10 .
    Hunter, DJ, Hankinson, SE, Laden, F.,  et al. 1997Plasma organochlorine levels and the risk of breast cancerN Engl J Med33712531258CrossRefPubMedGoogle Scholar
  11. 11.
    Liljegren, G, Hardell, L, Lindstrom, G, Dahl, P, Magnuson, A 1998Case-control study on breast cancer and adipose tissue concentrations of congener specific polychlorinated biphenyls, DDE and hexachlorobenzeneEur J Cancer Prev7135140PubMedGoogle Scholar
  12. 12.
    Mendonca, GA, Eluf-Neto, J, Andrada-Serpa, MJ.,  et al. 1999Organochlorines and breast cancer: a case-control study in BrazilInt J Cancer83596600CrossRefPubMedGoogle Scholar
  13. 13.
    Millikan, R, DeVoto, E, Duell, EJ.,  et al. 2000Dichlorodiphenyldichloroethene, polychlorinated biphenyls, and breast cancer among African-American and white women in North CarolinaCancer Epidemiol Biomarkers Prev912331240PubMedGoogle Scholar
  14. 14.
    Moysich, KB, Ambrosone, CB, Vena, JE.,  et al. 1998Environmental organochlorine exposure and postmenopausal breast cancer riskCancer Epidemiol Biomarkers Prev7181188PubMedGoogle Scholar
  15. 15.
    Mussalo-Rauhamaa, H, Hasanen, E, Pyysalo, H, Antervo, K, Kauppila, R, Pantzar, P 1990Occurrence of beta-hexachlorocyclohexane in breast cancer patientsCancer6621242128PubMedGoogle Scholar
  16. 16.
    Olaya-Contreras, P, Rodriguez-Villamil, J, Posso-Valencia, HJ, Cortez, JE 1998Organochlorine exposure and breast cancer risk in Colombian womenCad Saude Publica14125132Google Scholar
  17. 17.
    Romieu, I, Hernandez-Avila, M, Lazcano-Ponce, E, Weber, JP, Dewailly, E 2000Breast cancer, lactation history, and serum organochlorinesAm J Epidemiol152363370CrossRefPubMedGoogle Scholar
  18. 18.
    Schecter, A, Toniolo, P, Dai, LC, Thuy, LT, Wolff, MS 1997Blood levels of DDT and breast cancer risk among women living in the north of VietnamArch Environ Contam Toxicol33453456CrossRefPubMedGoogle Scholar
  19. 19.
    Stellman, SD, Djordjevic, MV, Britton, JA.,  et al. 2000Breast cancer risk in relation to adipose concentrations of organochlorine pesticides and polychlorinated biphenyls in Long Island, New YorkCancer Epidemiol Biomarkers Prev912411249PubMedGoogle Scholar
  20. 20.
    Unger, M, Kiaer, H, Blichert-Toft, M, Olsen, J, Clausen, J 1984Organochlorine compounds in human breast fat from deceased with and without breast cancer and in a biopsy material from newly diagnosed patients undergoing breast surgeryEnviron Res342428CrossRefPubMedGoogle Scholar
  21. 21.
    van’t Veer, P, Lobbezoo, IE, Martin-Moreno, JM.,  et al. 1997DDT (dicophane) and postmenopausal breast cancer in Europe: case-control studyBMJ3158185PubMedGoogle Scholar
  22. 22.
    Wolff, MS, Toniolo, PG, Lee, EW, Rivera, M, Dubin, N 1993Blood levels of organochlorine residues and risk of breast cancerJ Natl Cancer Inst85648652PubMedGoogle Scholar
  23. 23.
    Wolff, MS, Zeleniuch-Jacquotte, A, Dubin, N, Toniolo, P 2000Risk of breast cancer and organochlorine exposureCancer Epidemiol Biomarkers Prev9271277PubMedGoogle Scholar
  24. 24.
    Zheng, T, Holford, TR, Mayne, ST.,  et al. 1999Beta-benzene hexachloride in breast adipose tissue and risk of breast carcinomaCancer8522122218CrossRefPubMedGoogle Scholar
  25. 25.
    Zheng, T, Holford, TR, Mayne, ST.,  et al. 1999DDE and DDT in breast adipose tissue and risk of female breast cancerAm J Epidemiol150453458PubMedGoogle Scholar
  26. 26.
    Zheng, T, Holford, TR, Mayne, ST,  et al. 1999Environmental exposure to hexachlorobenzene (HCB) and risk of female breast cancer in ConnecticutCancer Epidemiol Biomarkers Prev8407411PubMedGoogle Scholar
  27. 27.
    Adami, HO, Lipworth, L, Titus-Ernstoff, L.,  et al. 1995Organochlorine compounds and estrogen-related cancers in womenCancer Causes Control6551566PubMedGoogle Scholar
  28. 28.
    Calle, EE, Frumkin, H, Henley, SJ, Savitz, DA, Thun, MJ 2002Organochlorines and breast cancer riskCA Cancer J Clin52301309PubMedGoogle Scholar
  29. 29.
    Ahlborg, UG, Lipworth, L, Titus-Ernstoff, L.,  et al. 1995Organochlorine compounds in relation to breast cancer, endometrial cancer, and endometriosis: an assessment of the biological and epidemiological evidenceCrit Rev Toxicol25463531PubMedGoogle Scholar
  30. 30.
    International Agency for Research on Cancer. IARC.1997Polychlorinated Dibenzo-para-dioxins and Polychlorinated Dibenzofurans IARC Monograph69World Health OrganizationLyon, FranceGoogle Scholar
  31. 31.
    Birnbaum, LS, Fenton, SE 2003Cancer and developmental exposure to endocrine disruptorsEnviron Health Perspect111389394PubMedGoogle Scholar
  32. 32.
    Krishnan, V, Safe, S 1993Polychlorinated biphenyls (PCBs), dibenzo- p-dioxins (PCDDs), and dibenzofurans (PCDFs) as antiestrogens in MCF-7 human breast cancer cells: quantitative structure–activity relationshipsToxicol Appl Pharmacol1205561PubMedGoogle Scholar
  33. 33.
    Safe, S, Astroff, B, Harris, M.,  et al. 19912,3,7,8-Tetrachlorodibenzo- p-dioxin (TCDD) and related compounds as antioestrogens: characterization and mechanism of actionPharmacol Toxicol69400409PubMedGoogle Scholar
  34. 34.
    White, TE, Gasiewicz, TA 1993The human estrogen receptor structural gene contains a DNA sequence that binds activated mouse and human Ah receptors: a possible mechanism of estrogen receptor regulation by 2,3,7,8-tetrachlorodibenzo- p-dioxinBiochem Biophys Res Commun193956962PubMedGoogle Scholar
  35. 35.
    Zacharewski, T, Harris, M, Safe, S 1991Evidence for the mechanism of action of the 2,3,7,8-tetrachlorodibenzo- p-dioxin-mediated decrease of nuclear estrogen receptor levels in wild-type and mutant mouse Hepa 1c1c7 cellsBiochem Pharmacol4119311939PubMedGoogle Scholar
  36. 36.
    Manz, A, Berger, J, Dwyer, JH, Flesch-Janys, D, Nagel, S, Waltsgott, H 1991Cancer mortality among workers in chemical plant contaminated with dioxinLancet338959964PubMedGoogle Scholar
  37. 37.
    Kogevinas, M, Saracci, R, Winkelmann, R.,  et al. 1993Cancer incidence and mortality in women occupationally exposed to chlorophenoxy herbicides, chlorophenols, and dioxinsCancer Causes Control4547553PubMedGoogle Scholar
  38. 38.
    Kogevinas, M, Becher, H, Benn, T.,  et al. 1997Cancer mortality in workers exposed to phenoxy herbicides, chlorophenols, and dioxins. An expanded and updated international cohort studyAm J Epidemiol14510611075PubMedGoogle Scholar
  39. 39.
    Lynge, E 1985A follow-up study of cancer incidence among workers in manufacture of phenoxy herbicides in DenmarkBr J Cancer52259270PubMedGoogle Scholar
  40. 40.
    Flesch-Janys, D, Berger, J, Gurn, P.,  et al. 1995Exposure to polychlorinated dioxins and furans (PCDD/F) and mortality in a cohort of workers from a herbicide-producing plant in Hamburg, Federal Republic of GermanyAm J Epidemiol14211651175PubMedGoogle Scholar
  41. 41.
    Warner, M, Eskenazi, B, Mocarelli, P.,  et al. 2002Serum dioxin concentrations and breast cancer risk in the Seveso Women’s Health StudyEnviron Health Perspect110625628Google Scholar
  42. 42.
    Bertazzi, A, Pesatori, AC, Consonni, D, Tironi, A, Landi, MT, Zocchetti, C 1993Cancer incidence in a population accidentally exposed to 2,3,7,8-tetrachlorodibenzo-para-dioxinEpidemiology4398406PubMedGoogle Scholar
  43. 43.
    Bertazzi, PA, Bernucci, I, Brambilla, G, Consonni, D, Pesatori, AC 1998The Seveso studies on early and long-term effects of dioxin exposure: a reviewEnviron Health Perspect106625633PubMedGoogle Scholar
  44. 44.
    Bertazzi, PA, Consonni, D, Bachetti, S.,  et al. 2001Health effects of dioxin exposure: a 20-year mortality studyAm J Epidemiol15310311044PubMedGoogle Scholar
  45. 45.
    Revich, B, Aksel, E, Ushakova, T.,  et al. 2001Dioxin exposure and public health in Chapaevsk, RussiaChemosphere43951966PubMedGoogle Scholar
  46. 46.
    Petreas, MX, She, J, Winkler, J.,  et al. 2000Organochlorine body burden in California populationsOrganohalogen Compounds481721Google Scholar
  47. 47.
    Petreas, M, Smith, D, Hurley, S, Jeffrey, SS, Gilliss, D, Reynolds, P 2004Distribution of persistent, lipid-soluble chemicals in breast and abdominal adipose tissues: lessons learned from a breast cancer studyCancer Epidemiol Biomarkers Prev13416424PubMedGoogle Scholar
  48. 48.
    Breslow, NE, Day, NE. 1980Statistical Methods in Cancer Research Vol. I. The Analysis of Case-Control StudiesInternational Agency for Research on CancerLyon, FranceGoogle Scholar
  49. 49.
    Hollander, M, Wolfe, DA 1973Nonparametric Statistical MethodsJohn Wiley & Sons IncNew YorkGoogle Scholar
  50. 50.
    North Atlantic Treaty Organization, Committee on Challenges of Modern Society (NATO/CCMS)1988International Toxicity Equivalent Factor (I-TEF) method of risk assessment for complex mixtures of dioxins and related compounds. Pilot Study on international information exchange on dioxins and related compoundsNorth Atlantic Treaty Organization, Committee on Challenges of Modern SocietyBrussels, BelgiumGoogle Scholar
  51. 51.
    Moysich, KB, Shields, PG, Freudenheim, JL.,  et al. 1999Polychlorinated biphenyls, cytochrome P4501A1 polymorphism, and postmenopausal breast cancer riskCancer Epidemiol Biomarkers Prev84144PubMedGoogle Scholar
  52. 52.
    SAS InstituteInc.,  2002SAS 8.2, 8.2 [computer program]SAS Institute IncCary, NCGoogle Scholar
  53. 53.
    Hardell, L, Lindstrom, G, Liljegren, G, Dahl, P, Magnuson, A 1996Increased concentrations of octachlorodibenzo- p-dioxin in cases with breast cancer – results from a case-control studyEur J Cancer Prev5351357PubMedGoogle Scholar
  54. 54.
    United States Environmental Protection Agency, National Center for Environmental Assessment (September 2000) Draft Exposure and Human Health Reassessment of 2,3,7,8-Tetrachlorodibenzo- p- Dioxin (TCDD) and Related Compounds [web page]. Available from =default, (Accessed 23 November 2004).Google Scholar
  55. 55.
    National Center for Environmental AssessmentExposure, Assessment, Risk Characterization, Group 2000Exposure to Human Health Reassessment of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related CompoundsU.S. Environmental Protection AgencyWashington DC, USAGoogle Scholar
  56. 56.
    Petreas, M, She, J, McKinney, M.,  et al. 2000

    Dioxin Body Burdens in California Populations

    Lipnick, R eds. Persistent Bioaccumulative Toxic Chemicals.American Chemical SocietyWashington, DC
    Google Scholar
  57. 57.
    Saracci, R, Kogevinas, M, Bertazzi, PA.,  et al. 1991Cancer mortality in workers exposed to chlorophenoxy herbicides and chlorophenolsLancet33810271032PubMedGoogle Scholar
  58. 58.
    Bertazzi, PA, Zocchetti, C, Guercilena, S.,  et al. 1997Dioxin exposure and cancer risk: a 15-year mortality study after the “Seveso accident”Epidemiology8646652PubMedGoogle Scholar
  59. 59.
    Bertazzi, PA, Zocchetti, C, Pesatori, AC, Guercilena, S, Sanarico, M, Radice, L 1989Ten-year mortality study of the population involved in the Seveso incident in 1976Am J Epidemiol12911871200PubMedGoogle Scholar
  60. 60.
    Mocarelli, P, Patterson, DJ, Marocchi, A, Needham, L 1990Pilot study (Phase II) for determining polychlorinated dibenzo-p-dioxin (PCDD) and polychlorinated dibenzofuran (PCDF) levels in serum of Seveso, Italy residents collected at the time of exposure: future plansChemosphere20967974Google Scholar
  61. 61.
    Marshall, LM, Hunter, DJ, Connolly, JL.,  et al. 1997Risk of breast cancer associated with atypical hyperplasia of lobular and ductal typesCancer Epidemiol Biomarkers Prev6297301PubMedGoogle Scholar
  62. 62.
    Vogel, VG 2004Atypia in the assessment of breast cancer risk: implications for managementDiagn Cytopathol30151157PubMedGoogle Scholar
  63. 63.
    Dupont, WD, Page, DL 1987Breast cancer risk associated with proliferative disease, age at first birth, and a family history of breast cancerAm J Epidemiol125769779PubMedGoogle Scholar
  64. 64.
    London, SJ, Connolly, JL, Schnitt, SJ, Colditz, GA 1992A prospective study of benign breast disease and the risk of breast cancerJAMA267941944PubMedGoogle Scholar
  65. 65.
    Bodian, CA, Perzin, KH, Lattes, R, Hoffmann, P, Abernathy, TG 1993Prognostic significance of benign proliferative breast diseaseCancer7138963907PubMedGoogle Scholar
  66. 66.
    Wang, J, Costantino, JP, Tan-Chiu, E, Wickerham, DL, Paik, S, Wolmark, N 2004Lower-category benign breast disease and the risk of invasive breast cancerJ Natl Cancer Inst96616620PubMedGoogle Scholar
  67. 67.
    Agency for Toxic Substances and Disease Registry1998Toxicological Profile for Chlorinated Dibenzo-p-dioxins (CDDs)U.S. Department of Health and Human Services, Public Health ServiceAtlanta, GA, USAGoogle Scholar
  68. 68.
    Potischman, N, Troisi, R 1999In-utero and early life exposures in relation to risk of breast cancerCancer Causes Control10561573PubMedGoogle Scholar
  69. 69.
    Okasha, M, McCarron, P, Gunnell, D, Smith, GD 2003Exposures in childhood, adolescence and early adulthood and breast cancer risk: a systematic review of the literatureBreast Cancer Res Treat78223276PubMedGoogle Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  • Peggy Reynolds
    • 1
  • Susan E. Hurley
    • 2
  • Myrto Petreas
    • 3
  • Debbie E. Goldberg
    • 2
  • Daniel Smith
    • 1
  • Debra Gilliss
    • 1
  • M. Ellen. Mahoney
    • 4
  • Stefanie S. Jeffrey
    • 4
  1. 1.California Department of Health ServicesEnvironmental Health Investigations BranchOaklandUSA
  2. 2.Public Health InstituteOaklandUSA
  3. 3.California Department of Toxic Substances ControlHazardous Materials LaboratoryBerkeleyUSA
  4. 4.Stanford University School of MedicineStanfordUSA

Personalised recommendations