Multiple xenoestrogen air pollutants and breast cancer risk: statistical approaches to investigate the combined exposures effect

Background and Aim: Despite that the population is exposed to a mixture of multiple air pollutants, the joint effect of these pollutants on breast cancer (BC) has never been investigated. We applied two new statistical approaches to assess the complex effect of exposure to a mixture of four xenoestrogen air pollutants (Benzo-[a]-pyrene (BaP), cadmium, dioxins, Polychlorinated Biphenyl 153(PCB153)) on the risk of BC. Methods: The study was conducted on 5,222 cases and 5,222 matched controls nested within the French national E3N cohort. Annual estimates of exposures to pollutants at participants’ addresses for each year from recruitment 1990 through 2011, were assessed using a chemistry transport model. Mean annual concentrations for each pollutant was then estimated from inclusion in the study to the index date. We fitted the bayesian kernel machine regression (BKMR) and the weighted quantile sum (WQS) regression models to estimate the risk of BC associated with the joint effect of co-exposure of four xenoestrogens air pollutants. Results: In BKMR, despite the no statistically significant association, there was an increasing trend between the joint effect and the risk of BC, when fixing other chemicals at their median concentrations. BaP, cadmium and PCB153 showed positive trends in the multi-pollutant mixture, while dioxin showed a modest inverse trend. In WQS, there was a borderline positive association between the WQS index of the joint effect and the risk of BC (odds ratio (OR)=1.06, 95% confidence intervals (CI):0.99-1.10). By menopausal status, there was a differential joint effect, with a significant positive association observed only in women who underwent menopausal transition (OR=1.09, 95% CI:1.02-1.14) Conclusions: Overall, although no clear association was observed with BKMR model, there was a tendency of an increased risk of BC associated with co-exposure to long-term xenoestrogens air pollutants using both approaches. Further studies are needed to confirm these findings.