ENVIRONMENTAL DDT EXPOSURE IN THE DEVELOPMENT OF BREAST CANCER

Abstract

DDT (dichlorodiphenyltrichloroethane), and one of its major metabolites, DDE (dichlorodiphenyldichloroethylene), exhibited estrogen effects in animal studies and observations on wildlife. Although the use of DDT has been banned for more than two decades, due to the long half-lives in the environment and bioconcentration through the food chain, their residues were still present in animal and human tissue. The endogenous estrogen, estradiol in the human body is metabolized via two pathways, one yields 2-hydroxyestrone (20HE1), which exhibits little peripheral biological activity. The other leads to 16a-hydroxyestrone (160HE1), a strong estrogen that damages the DNA. Inconsistent results were reported in six small-scale case-control studies examining the relationship between DDT exposure and breast cancer. No studies that looking into the interaction of DDT/DOE and estrogen metabolism in breast cancer surveys are found in current literature search. The aims of the present research were to study: (I) the relationship of the serum DDT or DDE with the metabolism of endogenic estrogen; (2) the association of the serum DDT or DDE with the breast cancer; (3) the association of the urinary 20HE1 with breast cancer; (4) the association of the urinary 160HE1 with breast cancer; (5) the association of the urinary 20HE1/160HE1 ratio with breast cancer.

A case-control study design was used to elucidate the effect of DDT exposure on cstrogen (n=73) metabolism and breast cancer. Seventy three (73) cases or breast cancer studied were pathologically confirmed hospital cases. Two control groups, fifty (50) cancer free breast disease patients and seventy-four (74) samples taken from general populations, were included in the study. Serum DDT/ODE levels were quantified by GC-ECD and the ratio of urinary 2/160HE1 by enzyme immunoassay (ElA).

Significantly higher levels of blood DDT and ODE were found in the breast cancer group than those in the controls (p<0.05). Urinary 2OHE1 level in breast cancer group was 40-48% lower than controls (p<0.05), and the urinary 16OHE1 level in breast cancer group was 80%-130% higher (p<0.05). As a result, the ratio of 2/16OHE1 for breast cancer group was 2.8 - 3.4 times lower than the controls (p<0.0001 ). No association was found between the blood DDT or DOE level and the urinary estrogenic metabolites. High sensitivity and specificity (62.3% and 81.3%) were observed for 2/16O1-IE 1 as a breast cancer biomarker.

These results strongly suggested that DDT/ODE and unnary 16OHE1 were risk factors for breast cancer. The induction of breast cancer by the exposure to DDT and estogenic metabolism appeared to be effected through independent mechanisms. The ratio of urinary 2/16OHE1 could be a good biomarker for predicting breast cancer risk.