Blood levels of organochlorine residues and risk of breast cancer.

Organochlorines such as DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] and PCBs (polychlorinated biphenyls), which have been used extensively as insecticides and as fluid insulators of electrical components, respectively, are known to be persistent environmental contaminants and animal carcinogens. These agents have been found in human tissue due to their inefficient metabolism and their solubility in lipids, which lead to lifelong sequestration in adipose tissue. Their association with human cancer occurrence, however, has been explored only marginally, with most studies having 20 or fewer cases. This blinded study was designed to determine whether exposure to PCBs and to DDE [1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene], the major metabolite of DDT, is associated with breast cancer risk in women. We analyzed sera from the stored blood specimens of 14,290 participants enrolled between 1985 and 1991 in the New York University Women's Health Study, a prospective cohort study of hormones, diet, and cancer. Cohort members who developed breast cancer were included as case patients in our nested case-control study. DDE and PCBs were measured by gas chromatography in the sera of 58 women with a diagnosis of breast cancer 1-6 months after they entered the cohort and in 171 matched control subjects from the same study population who did not develop cancer. Mean levels of DDE and PCBs were higher for breast cancer case patients than for control subjects, but paired differences were statistically significant only for DDE (P = .031). After adjustment for first-degree family history of breast cancer, lifetime lactation, and age at first full-term pregnancy, conditional logistic regression analysis showed a fourfold increase in relative risk of breast cancer for an elevation of serum DDE concentrations from 2.0 ng/mL (10th percentile) to 19.1 ng/mL (90th percentile). For PCBs, the relative risk for a change in serum levels from 3.9 ng/mL (10th percentile) to 10.6 ng/mL (90th percentile) was less than twofold, a nonsignificant association that was further reduced after adjustment for DDE. In this population of New York City women, breast cancer was strongly associated with DDE in serum but not with PCBs. These findings suggest that environmental chemical contamination with organochlorine residues may be an important etiologic factor in breast cancer. Given the widespread dissemination of organochlorine insecticides in the environment and the food chain, the implications are far-reaching for public health intervention worldwide.