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

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.