Superfund Research Program
Organochlorine Exposure and Breast Cancer Risk
Breast cancer is a leading cause of cancer mortality among women in the United States and Europe. It is well recognized that age, family history, and reproductive history are major risk factors for developing the disease. However, much less is known about the role that environmental agents play in the initiation, promotion, and/or progression of breast cancer.
A group of widespread and persistent environmental chemicals known as "organochlorines" has been of particular interest in breast cancer etiology because a number of these compounds appear to mimic hormones and thus have a strong potential to influence growth processes in the body. Some researchers hypothesize that these chemicals exert their effects early in the multi-step process of breast cancer by acting as tumor promoters through mechanisms involving the estrogen receptor. Thus, the timing of exposure to organochlorines is thought to be critical. If this is the case, then the critical exposure period may occur far in advance of the diagnosis of the disease. However, evaluating this relationship has been difficult because exposure data are typically not available for the period before breast cancer develops.
Researchers in the Boston University Superfund Basic Research Program, in cooperation with the Copenhagen Center for Prospective Studies, took advantage of a unique resource of banked serum samples to investigate the relationship between organochlorine exposures and the development of breast cancer. The U.S. Centers for Disease Control and Prevention (CDC) carried out analyses of the serum samples, which were collected more than 20 years ago, to determine body burdens of organochlorine compounds in a group of women who were later diagnosed with breast cancer. For comparison, serum was also analyzed in a group of healthy controls.
The banked serum samples were originally gathered for the Copenhagen City Heart Study (CCHS), which was initiated in 1976 to investigate risk factors for cardiovascular diseases. Approximately 7,500 Danish women aged 30-75 years had blood samples taken, a portion of which was frozen and stored. Using the Danish Cancer Registry, which records all cases of cancer in the Danish population, investigators identified two hundred sixty-eight women who had developed breast cancer between the initiation of the CCHS and 1993. From the remaining cohort, two surviving control subjects for each case were matched on age, date of examination, and vital statistics at the time of case diagnosis.
Eighty-nine percent of the selected study subjects (i.e., 240 cases and 477 controls) had serum samples available for organochlorine analysis. The serum samples were analyzed for 18 pesticides and their metabolites, and 28 different polychlorinated biphenyl (PCB) congeners by the Environmental Health Laboratory Division at the CDC in Atlanta, Georgia.
In the chemical analysis of the blood samples most organochlorines investigated were found. The most lipophilic and environmentally persistent compounds were detected in a majority of the samples. For example, dieldrin was found in 78 % of the serum samples, PCB congeners in 98.5%, and DDT compounds in 100%. The statistical evaluation of the first part of this study has just been completed.
Previous studies on DDT and PCBs have shown conflicting results. The findings of this study showed no clear association between serum concentrations of DDT or PCBs and breast cancer risk.
However, the study also showed that women with the highest serum levels of dieldrin had at least a doubled risk of breast cancer compared to women with the lowest levels. Dieldrin has shown estrogenic activity in in vitro assays. The strong relationship of breast cancer risk with past exposure to dieldrin, an organochlorine compound showing estrogenic activity in vitro, supports the hypothesis that exposure to endocrine-disrupting organochlorines may increase the risk of breast cancer.
Concern over the hormonal activity of certain environmentally persistent organochlorines has raised important questions about the potential of these chemicals to increase breast cancer risk. This study is significant for evaluating the relationship between pre-disease levels of organochlorines in the body and subsequent development of breast cancer. The findings of this research should help clarify the role of organochlorines in the etiology of breast cancer.
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To learn more about this research, please refer to the following sources:
- Hoyer AP, Grandjean P, Jorgensen T, Brock JW, Hartvig HB. 1998. Organochlorine exposure and risk of breast cancer. Lancet 352(9143):1816-1820. PMID:9851382
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