Background: Air pollution is a complex mixture of correlated compounds, some with endocrine-disrupting properties capable of interfering with hormonal regulation and potentially influencing cancer risk. However, most epidemiological studies assessed single pollutants, limiting understanding of combined effects.
Objectives: We developed a novel Multiple Air Pollutants Index (MAPI), biologically informed and weighted using toxicological bioactivity data, to assess cumulative exposure and its association with breast cancer risk.
Methods: Long-term exposure to four endocrine-disrupting pollutants (benzo[a]pyrene (BaP), cadmium, dioxin, polychlorinated biphenyl153 (PCB153)) was estimated at consecutive residential addresses (1990–2011) of 5,222 breast cancer cases and 5,222 matched controls from the French E3N-Generations cohort, using the CHIMERE atmospheric model. The MAPI summed pollutant concentrations weighted by AC50-derived bioactivity for breast cancer–relevant targets from the US EPA's ToxCast database. Multivariable conditional logistic regression, adjusted for confounders, estimated odds ratios (ORs) and 95% confidence intervals (CIs).
Results A one standard deviation increase in MAPI was associated with higher breast cancer risk overall (OR = 1.18; CI: 1.09-1.29). Positive associations were observed among postmenopausal women (OR = 1.14; CI: 1.00-1.30) and women transitioning to menopause (OR = 1.20; CI: 1.04-1.38), with higher MAPI levels linked to increased risk of hormone receptor–positive breast cancers (ER+, PR+, ER+/PR+), poorly differentiated (Grade III) and invasive ductal tumors.
Conclusions/Implications: This study supports a link between exposure to multiple air pollutants and breast cancer risk. By integrating toxicological bioactivity data with atmospheric modeling, the MAPI provides a novel framework for assessing health effects of complex pollutant mixtures in environmental epidemiology and risk assessment.