Skip to main content
PMC home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 2004 Feb;112(2):207–214. doi: 10.1289/ehp.112-1241830

Dichlorodiphenyldichloroethane burden and breast cancer risk: a meta-analysis of the epidemiologic evidence.

Malaquías López-Cervantes 1, Luisa Torres-Sánchez 1, Aurelio Tobías 1, Lizbeth López-Carrillo 1
PMCID: PMC1241830  PMID: 14754575

Abstract

The relationship of dichlorodiphenyltrichloroethane (DDT) exposure and breast cancer risk has received increasing attention since the beginning of the 1990s. Contradicting published results regarding the relationship between body burden levels of p,p'-dichlorodiphenyldichloroethane (p,p'-DDE)--the main DDT metabolite--and breast cancer, we argue that such differences stem from methodologic differences among those studies. We performed a meta-analysis of 22 articles using DerSimonian and Laird's method for random effects models. The Q-statistic was used to identify heterogeneity in the outcome variable across studies. The gradient of p,p'-DDE exposure in epidemiologic studies was homogenized to serum lipid bases (nanograms per gram). The potential for publication bias was examined by means of the Begg's test. We discuss methodologic features of the studies in an attempt to reconcile the findings. The summary odds ratio (OR) for selected studies was 0.97 (95% confidence interval, 0.87-1.09) and the gradient of exposure ranged from 84.37 to 12,948 ng/g. No overall heterogeneity in the OR was observed (chi-squared = 27.93; df = 23; p = 0.218). Neither the study design nor the lack of breast-feeding control or the type of biologic specimen used to measure p,p'-DDE levels were the causes of heterogeneity throughout the studies. Evidence for publication bias was not found (p = 0.253). Overall, these results should be regarded as a strong evidence to discard the putative relationship between p,p'-DDE and breast cancer risk. Nevertheless, the exposure to DDT during critical periods of human development--from conception to adolescence--and individual variations in metabolizing enzymes of DDT or its derivatives are still important areas to be researched in regard to breast cancer development in adulthood.

Full Text

The Full Text of this article is available as a PDF (216.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aronson K. J., Miller A. B., Woolcott C. G., Sterns E. E., McCready D. R., Lickley L. A., Fish E. B., Hiraki G. Y., Holloway C., Ross T. Breast adipose tissue concentrations of polychlorinated biphenyls and other organochlorines and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2000 Jan;9(1):55–63. [PubMed] [Google Scholar]
  2. Austin H., Keil J. E., Cole P. A prospective follow-up study of cancer mortality in relation to serum DDT. Am J Public Health. 1989 Jan;79(1):43–46. doi: 10.2105/ajph.79.1.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bagga D., Anders K. H., Wang H. J., Roberts E., Glaspy J. A. Organochlorine pesticide content of breast adipose tissue from women with breast cancer and control subjects. J Natl Cancer Inst. 2000 May 3;92(9):750–753. doi: 10.1093/jnci/92.9.750. [DOI] [PubMed] [Google Scholar]
  4. Begg C. B. A measure to aid in the interpretation of published clinical trials. Stat Med. 1985 Jan-Mar;4(1):1–9. doi: 10.1002/sim.4780040103. [DOI] [PubMed] [Google Scholar]
  5. Begg C. B., Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994 Dec;50(4):1088–1101. [PubMed] [Google Scholar]
  6. Berkey C. S., Hoaglin D. C., Mosteller F., Colditz G. A. A random-effects regression model for meta-analysis. Stat Med. 1995 Feb 28;14(4):395–411. doi: 10.1002/sim.4780140406. [DOI] [PubMed] [Google Scholar]
  7. Dello Iacovo R., Celentano E., Strollo A. M., Iazzetta G., Capasso I., Randazzo G. Organochlorines and breast cancer. A study on Neapolitan women. Adv Exp Med Biol. 1999;472:57–66. [PubMed] [Google Scholar]
  8. Demers A., Ayotte P., Brisson J., Dodin S., Robert J., Dewailly E. Risk and aggressiveness of breast cancer in relation to plasma organochlorine concentrations. Cancer Epidemiol Biomarkers Prev. 2000 Feb;9(2):161–166. [PubMed] [Google Scholar]
  9. DerSimonian R., Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986 Sep;7(3):177–188. doi: 10.1016/0197-2456(86)90046-2. [DOI] [PubMed] [Google Scholar]
  10. Dewailly E., Dodin S., Verreault R., Ayotte P., Sauvé L., Morin J., Brisson J. High organochlorine body burden in women with estrogen receptor-positive breast cancer. J Natl Cancer Inst. 1994 Feb 2;86(3):232–234. doi: 10.1093/jnci/86.3.232. [DOI] [PubMed] [Google Scholar]
  11. Dorgan J. F., Brock J. W., Rothman N., Needham L. L., Miller R., Stephenson H. E., Jr, Schussler N., Taylor P. R. Serum organochlorine pesticides and PCBs and breast cancer risk: results from a prospective analysis (USA). Cancer Causes Control. 1999 Feb;10(1):1–11. doi: 10.1023/a:1008824131727. [DOI] [PubMed] [Google Scholar]
  12. Duell E. J., Millikan R. C., Savitz D. A., Newman B., Smith J. C., Schell M. J., Sandler D. P. A population-based case-control study of farming and breast cancer in North Carolina. Epidemiology. 2000 Sep;11(5):523–531. doi: 10.1097/00001648-200009000-00007. [DOI] [PubMed] [Google Scholar]
  13. Falck F., Jr, Ricci A., Jr, Wolff M. S., Godbold J., Deckers P. Pesticides and polychlorinated biphenyl residues in human breast lipids and their relation to breast cancer. Arch Environ Health. 1992 Mar-Apr;47(2):143–146. [PubMed] [Google Scholar]
  14. Fleming L. E., Bean J. A., Rudolph M., Hamilton K. Cancer incidence in a cohort of licensed pesticide applicators in Florida. J Occup Environ Med. 1999 Apr;41(4):279–288. doi: 10.1097/00043764-199904000-00010. [DOI] [PubMed] [Google Scholar]
  15. Galván-Portillo Marcia, Jiménez-Gutiérrez Carlos, Torres-Sánchez Luisa, López-Carrillo Lizbeth. Food consumption and adipose tissue DDT levels in Mexican women. Cad Saude Publica. 2002 Mar-Apr;18(2):447–452. doi: 10.1590/s0102-311x2002000200009. [DOI] [PubMed] [Google Scholar]
  16. Güttes S., Failing K., Neumann K., Kleinstein J., Georgii S., Brunn H. Chlororganic pesticides and polychlorinated biphenyls in breast tissue of women with benign and malignant breast disease. Arch Environ Contam Toxicol. 1998 Jul;35(1):140–147. doi: 10.1007/s002449900361. [DOI] [PubMed] [Google Scholar]
  17. Helzlsouer K. J., Alberg A. J., Huang H. Y., Hoffman S. C., Strickland P. T., Brock J. W., Burse V. W., Needham L. L., Bell D. A., Lavigne J. A. Serum concentrations of organochlorine compounds and the subsequent development of breast cancer. Cancer Epidemiol Biomarkers Prev. 1999 Jun;8(6):525–532. [PubMed] [Google Scholar]
  18. Hunter D. J., Hankinson S. E., Laden F., Colditz G. A., Manson J. E., Willett W. C., Speizer F. E., Wolff M. S. Plasma organochlorine levels and the risk of breast cancer. N Engl J Med. 1997 Oct 30;337(18):1253–1258. doi: 10.1056/NEJM199710303371801. [DOI] [PubMed] [Google Scholar]
  19. Høyer A. P., Grandjean P., Jørgensen T., Brock J. W., Hartvig H. B. Organochlorine exposure and risk of breast cancer. Lancet. 1998 Dec 5;352(9143):1816–1820. doi: 10.1016/S0140-6736(98)04504-8. [DOI] [PubMed] [Google Scholar]
  20. Høyer A. P., Jørgensen T., Brock J. W., Grandjean P. Organochlorine exposure and breast cancer survival. J Clin Epidemiol. 2000 Mar 1;53(3):323–330. doi: 10.1016/s0895-4356(99)00165-1. [DOI] [PubMed] [Google Scholar]
  21. Høyer A. P., Jørgensen T., Grandjean P., Hartvig H. B. Repeated measurements of organochlorine exposure and breast cancer risk (Denmark). Cancer Causes Control. 2000 Feb;11(2):177–184. doi: 10.1023/a:1008926219539. [DOI] [PubMed] [Google Scholar]
  22. Krieger N., Wolff M. S., Hiatt R. A., Rivera M., Vogelman J., Orentreich N. Breast cancer and serum organochlorines: a prospective study among white, black, and Asian women. J Natl Cancer Inst. 1994 Apr 20;86(8):589–599. doi: 10.1093/jnci/86.8.589. [DOI] [PubMed] [Google Scholar]
  23. Laden F., Collman G., Iwamoto K., Alberg A. J., Berkowitz G. S., Freudenheim J. L., Hankinson S. E., Helzlsouer K. J., Holford T. R., Huang H. Y. 1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene and polychlorinated biphenyls and breast cancer: combined analysis of five U.S. studies. J Natl Cancer Inst. 2001 May 16;93(10):768–776. doi: 10.1093/jnci/93.10.768. [DOI] [PubMed] [Google Scholar]
  24. Laden F., Hankinson S. E., Wolff M. S., Colditz G. A., Willett W. C., Speizer F. E., Hunter D. J. Plasma organochlorine levels and the risk of breast cancer: an extended follow-up in the Nurses' Health Study. Int J Cancer. 2001 Feb 15;91(4):568–574. doi: 10.1002/1097-0215(200002)9999:9999<::aid-ijc1081>3.0.co;2-w. [DOI] [PubMed] [Google Scholar]
  25. Liljegren G., Hardell L., Lindström G., Dahl P., Magnuson A. Case-control study on breast cancer and adipose tissue concentrations of congener specific polychlorinated biphenyls, DDE and hexachlorobenzene. Eur J Cancer Prev. 1998 Apr;7(2):135–140. [PubMed] [Google Scholar]
  26. López-Carrillo L., Blair A., López-Cervantes M., Cebrián M., Rueda C., Reyes R., Mohar A., Bravo J. Dichlorodiphenyltrichloroethane serum levels and breast cancer risk: a case-control study from Mexico. Cancer Res. 1997 Sep 1;57(17):3728–3732. [PubMed] [Google Scholar]
  27. López-Carrillo L., Torres-Sánchez L., López-Cervantes M., Blair A., Cebrián M. E., Uribe M. The adipose tissue to serum dichlorodiphenyldichloroethane (DDE) ratio: some methodological considerations. Environ Res. 1999 Aug;81(2):142–145. doi: 10.1006/enrs.1999.3961. [DOI] [PubMed] [Google Scholar]
  28. López-Carrillo L., Torres-Sánchez L., Moline J., Ireland K., Wolff M. S. Breast-feeding and serum p,p'DDT levels among Mexican women of childbearing age: a pilot study. Environ Res. 2001 Dec;87(3):131–135. doi: 10.1006/enrs.2001.4296. [DOI] [PubMed] [Google Scholar]
  29. Mendonça G. A., Eluf-Neto J., Andrada-Serpa M. J., Carmo P. A., Barreto H. H., Inomata O. N., Kussumi T. A. Organochlorines and breast cancer: a case-control study in Brazil. Int J Cancer. 1999 Nov 26;83(5):596–600. doi: 10.1002/(sici)1097-0215(19991126)83:5<596::aid-ijc4>3.0.co;2-p. [DOI] [PubMed] [Google Scholar]
  30. Millikan R., DeVoto E., Duell E. J., Tse C. K., Savitz D. A., Beach J., Edmiston S., Jackson S., Newman B. Dichlorodiphenyldichloroethene, polychlorinated biphenyls, and breast cancer among African-American and white women in North Carolina. Cancer Epidemiol Biomarkers Prev. 2000 Nov;9(11):1233–1240. [PubMed] [Google Scholar]
  31. Moysich K. B., Ambrosone C. B., Vena J. E., Shields P. G., Mendola P., Kostyniak P., Greizerstein H., Graham S., Marshall J. R., Schisterman E. F. Environmental organochlorine exposure and postmenopausal breast cancer risk. Cancer Epidemiol Biomarkers Prev. 1998 Mar;7(3):181–188. [PubMed] [Google Scholar]
  32. Olaya-Contreras P., Rodríguez-Villamil J., Posso-Valencia H. J., Cortez J. E. Organochlorine exposure and breast cancer risk in Colombian women. Cad Saude Publica. 1998;14 (Suppl 3):125–132. doi: 10.1590/s0102-311x1998000700013. [DOI] [PubMed] [Google Scholar]
  33. Phillips D. L., Pirkle J. L., Burse V. W., Bernert J. T., Jr, Henderson L. O., Needham L. L. Chlorinated hydrocarbon levels in human serum: effects of fasting and feeding. Arch Environ Contam Toxicol. 1989 Jul-Aug;18(4):495–500. doi: 10.1007/BF01055015. [DOI] [PubMed] [Google Scholar]
  34. Romieu I., Hernandez-Avila M., Lazcano-Ponce E., Weber J. P., Dewailly E. Breast cancer, lactation history, and serum organochlorines. Am J Epidemiol. 2000 Aug 15;152(4):363–370. doi: 10.1093/aje/152.4.363. [DOI] [PubMed] [Google Scholar]
  35. Romieu I., Hernández-Avila M., Lazcano E., Lopez L., Romero-Jaime R. Breast cancer and lactation history in Mexican women. Am J Epidemiol. 1996 Mar 15;143(6):543–552. doi: 10.1093/oxfordjournals.aje.a008784. [DOI] [PubMed] [Google Scholar]
  36. Schecter A., Toniolo P., Dai L. C., Thuy L. T., Wolff M. S. Blood levels of DDT and breast cancer risk among women living in the north of Vietnam. Arch Environ Contam Toxicol. 1997 Nov;33(4):453–456. doi: 10.1007/s002449900276. [DOI] [PubMed] [Google Scholar]
  37. Snedeker S. M. Pesticides and breast cancer risk: a review of DDT, DDE, and dieldrin. Environ Health Perspect. 2001 Mar;109 (Suppl 1):35–47. doi: 10.1289/ehp.01109s135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Stellman S. D., Djordjevic M. V., Britton J. A., Muscat J. E., Citron M. L., Kemeny M., Busch E., Gong L. Breast cancer risk in relation to adipose concentrations of organochlorine pesticides and polychlorinated biphenyls in Long Island, New York. Cancer Epidemiol Biomarkers Prev. 2000 Nov;9(11):1241–1249. [PubMed] [Google Scholar]
  39. Talbott E. O., Zborowski J. V., Kuller L. H. Organochlorine residues and breast cancer. N Engl J Med. 1998 Apr 2;338(14):988–991. [PubMed] [Google Scholar]
  40. Torres-Arreola L., López-Carrillo L., Torres-Sánchez L., Cebrián M., Rueda C., Reyes R., López-Cervantes M. Levels of dichloro-dyphenyl-trichloroethane (DDT) metabolites in maternal milk and their determinant factors. Arch Environ Health. 1999 Mar-Apr;54(2):124–129. doi: 10.1080/00039899909602247. [DOI] [PubMed] [Google Scholar]
  41. Torres-Arreola Laura, Berkowitz Gertrud, Torres-Sánchez Luisa, López-Cervantes Malaquías, Cebrián Mariano E., Uribe Marisela, López-Carrillo Lizbeth. Preterm birth in relation to maternal organochlorine serum levels. Ann Epidemiol. 2003 Mar;13(3):158–162. doi: 10.1016/s1047-2797(02)00424-6. [DOI] [PubMed] [Google Scholar]
  42. Turusov Vladimir, Rakitsky Valery, Tomatis Lorenzo. Dichlorodiphenyltrichloroethane (DDT): ubiquity, persistence, and risks. Environ Health Perspect. 2002 Feb;110(2):125–128. doi: 10.1289/ehp.02110125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Unger M., Kiaer H., Blichert-Toft M., Olsen J., Clausen J. Organochlorine compounds in human breast fat from deceased with and without breast cancer and in a biopsy material from newly diagnosed patients undergoing breast surgery. Environ Res. 1984 Jun;34(1):24–28. doi: 10.1016/0013-9351(84)90072-0. [DOI] [PubMed] [Google Scholar]
  44. Unger M., Olsen J., Clausen J. Organochlorine compounds in the adipose tissue of deceased persons with and without cancer: a statistical survey of some potential confounders. Environ Res. 1982 Dec;29(2):371–376. doi: 10.1016/0013-9351(82)90038-x. [DOI] [PubMed] [Google Scholar]
  45. Verma S. P., Salamone E., Goldin B. Curcumin and genistein, plant natural products, show synergistic inhibitory effects on the growth of human breast cancer MCF-7 cells induced by estrogenic pesticides. Biochem Biophys Res Commun. 1997 Apr 28;233(3):692–696. doi: 10.1006/bbrc.1997.6527. [DOI] [PubMed] [Google Scholar]
  46. Ward E. M., Schulte P., Grajewski B., Andersen A., Patterson D. G., Jr, Turner W., Jellum E., Deddens J. A., Friedland J., Roeleveld N. Serum organochlorine levels and breast cancer: a nested case-control study of Norwegian women. Cancer Epidemiol Biomarkers Prev. 2000 Dec;9(12):1357–1367. [PubMed] [Google Scholar]
  47. Wassermann M., Nogueira D. P., Tomatis L., Mirra A. P., Shibata H., Arie G., Cucos S., Wassermann D. Organochlorine compounds in neoplastic and adjacent apparently normal breast tissue. Bull Environ Contam Toxicol. 1976 Apr;15(4):478–484. doi: 10.1007/BF01685076. [DOI] [PubMed] [Google Scholar]
  48. Wolff M. S., Berkowitz G. S., Brower S., Senie R., Bleiweiss I. J., Tartter P., Pace B., Roy N., Wallenstein S., Weston A. Organochlorine exposures and breast cancer risk in New York City women. Environ Res. 2000 Oct;84(2):151–161. doi: 10.1006/enrs.2000.4075. [DOI] [PubMed] [Google Scholar]
  49. Wolff M. S., Toniolo P. G., Lee E. W., Rivera M., Dubin N. Blood levels of organochlorine residues and risk of breast cancer. J Natl Cancer Inst. 1993 Apr 21;85(8):648–652. doi: 10.1093/jnci/85.8.648. [DOI] [PubMed] [Google Scholar]
  50. Wolff M. S., Zeleniuch-Jacquotte A., Dubin N., Toniolo P. Risk of breast cancer and organochlorine exposure. Cancer Epidemiol Biomarkers Prev. 2000 Mar;9(3):271–277. [PubMed] [Google Scholar]
  51. Zheng T., Holford T. R., Mayne S. T., Tessari J., Ward B., Carter D., Owens P. H., Boyle P., Dubrow R., Archibeque-Engle S. Risk of female breast cancer associated with serum polychlorinated biphenyls and 1,1-dichloro-2,2'-bis(p-chlorophenyl)ethylene. Cancer Epidemiol Biomarkers Prev. 2000 Feb;9(2):167–174. [PubMed] [Google Scholar]
  52. Zheng T., Holford T. R., Mayne S. T., Ward B., Carter D., Owens P. H., Dubrow R., Zahm S. H., Boyle P., Archibeque S. DDE and DDT in breast adipose tissue and risk of female breast cancer. Am J Epidemiol. 1999 Sep 1;150(5):453–458. doi: 10.1093/oxfordjournals.aje.a010033. [DOI] [PubMed] [Google Scholar]
  53. van't Veer P., Lobbezoo I. E., Martín-Moreno J. M., Guallar E., Gómez-Aracena J., Kardinaal A. F., Kohlmeier L., Martin B. C., Strain J. J., Thamm M. DDT (dicophane) and postmenopausal breast cancer in Europe: case-control study. BMJ. 1997 Jul 12;315(7100):81–85. doi: 10.1136/bmj.315.7100.81. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES