Serum Concentrations of Organochlorine Compounds and the Subsequent Development of Breast Cancer

Kathy J. Helzlsouer; Anthony J. Alberg; Han-Yao Huang; Sandra C. Hoffman; Paul T. Strickland; John W. Brock; Virlyn W. Burse; Larry L. Needham; Douglas A. Bell; Jackie A. Lavigne; James D. Yager; George W. Comstock

DOI: Published June 1999

Abstract

A nested case-control study was conducted to examine the association between serum concentrations of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), the primary metabolite of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), and polychlorinated biphenyls (PCBs) and the development of breast cancer up to 20 years later. Cases (n = 346) and controls (n = 346) were selected from cohorts of women who donated blood in 1974, 1989, or both, and were matched on age, race, menopausal status, and month and year of blood donation. Analyses were stratified by cohort participation because median DDE and PCB concentrations among the controls were 59 and 147% higher in 1974 than 1989, respectively. Median concentrations of DDE were lower among cases than controls in both time periods [11.7% lower in 1974 (P = 0.06) and 8.6% lower in 1989 (P = 0.41)]. Median concentrations of PCBs were similar among cases and controls [P = 0.21 for 1974 and P = 0.37 for 1989 (Wilcoxon signed rank test)]. The risk of developing breast cancer among women with the highest concentrations of DDE was roughly half that among women with the lowest concentrations, whether based on concentrations in 1974 [odds ratio (OR), 0.50; 95% confidence interval (CI), 0.27–0.89; P_trend = 0.02] or in 1989 (OR, 0.53; 95% CI, 0.24–1.17; P_trend = 0.08). The associations between circulating concentrations of PCBs and breast cancer were less pronounced but still in the same direction (1974: OR, 0.68; 95% CI, 0.36–12.9; P_trend = 0.2; and 1989: OR, 0.73; 95% CI, 0.37–1.46; P_trend = 0.6). Adjustment for family history of breast cancer, body mass index, age at menarche or first birth, and months of lactation did not materially alter these associations. These associations remained consistent regardless of lactation history and length of the follow-up interval, with the strongest inverse association observed among women diagnosed 16–20 years after blood drawing. Results from this prospective, community-based nested case-control study are reassuring. Even after 20 years of follow-up, exposure to relatively high concentrations of DDE or PCBs showed no evidence of contributing to an increased risk of breast cancer.

Footnotes

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↵1 Supported by National Cancer Institute Grant CA62988, Department of Defense Grant DAMD17-94-J-4265, Career Research Award (to G. W. C.), National Heart, Lung and Blood Institute Grant HL21670, and National Institute of Environmental Health Sciences Grant ES03819.
↵2 To whom requests for reprints should be addressed, at Department of Epidemiology, The Johns Hopkins University School of Hygiene and Public Health, Room E-6132, 615 North Wolfe Street, Baltimore, MD 21205. Phone: (410) 955-9727; Fax: (410) 614-2632.
↵3 The abbreviations used are: DDE, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene; DDT, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane; PCB, polychlorinated biphenyl; COMT, catechol-O-methyltransferase; CLUE I, Campaign against Cancer and Stroke; CLUE II, Campaign against Cancer and Heart Disease; OR, odds ratio; CI, confidence interval; GT, glutathione.
- Accepted May 4, 1999.
- Received November 10, 1998.
- Revision received April 30, 1999.