Biological concentrations of DDT metabolites and breast cancer risk: an updated systematic review and meta-analysis

The question of whether dichlorodiphenyltrichloroethane (DDT) exposure is related to breast cancer (BC) remains unanswered, possibly due to methodological constraints in the studies that have been performed. We aimed to update and synthesize the available epidemiological evidence on the relationship of p,p'-DDT, o,p'-DDT and p,p'-dichlorodiphenyldichloroethylene (p,p'- DDE) biological concentrations with female BC, focusing in methodological characteristics not addressed in previous reviews. We conducted an overview of reviews and a systematic review and meta-analysis. We used six databases and one search engine to identify meta-analyses based on systematic reviews, pooled analyses, and individual studies published from January 2000 to December 2021. For the overview of reviews, we assessed meta-analyses' risk of bias and carried out a narrative synthesis. For the meta-analysis, we estimated summary association measures with fixed or random effects models for each compound stratifying for characteristics of interest. We estimated a positive summary association between p,p'- DDT biological concentrations and BC in prospective studies (nested case control) with >10 years of follow-up (sOR=1.41; 95 %CI: 1.06-1.88). Among retrospective studies (hospital or population-based case-control), BC was positively related with p,p'-DDE biological concentrations (sOR=1.15; 95 %CI: 1.02-1.30), and with p,p'-DDT in women with mean serum concentrations>100 ng/g (sOR=1.33; 95 %CI: 1.25-1.41). Moreover, we detected a positive association between o,p'-DDT and BC (sOR=2.24; 95 %CI: 2.15-2.34). Our results support a positive relationship between DDT exposure and BC, and are useful to reinforce its worldwide prohibition, since this pesticide is still used in some countries, has long persistence in the human body and disseminates to other geographic areas.