PM2.5 exposure and breast cancer risk

Background: Exposure to fine particulate matter (PM2.5) is increasingly recognized as a breast cancer risk factor, yet its combined effect with genetic susceptibility is unclear. This study examined the effects of PM2.5 and genetic variants ESR1 (Estrogen Receptor 1) rs2046210 and FGFR2 (Fibroblast Growth Factor Receptor 2) rs2981582 on breast cancer risk. Methods: Data from the Taiwan Biobank included 649 breast cancer cases and 69,403 controls. PM2.5 exposure was estimated using a hybrid Kriging-land-use regression model. Genetic variants were genotyped using TWB arrays. Logistic regression analyzed independent and combined effects, with a ten-fold sensitivity analysis assessing result robustness. Results: ESR1 rs2046210 (AA: OR = 1.67, 95% CI: 1.33–2.10) and FGFR2 rs2981582 (AA: OR = 1.51, 95% CI: 1.18–1.93) significantly increased risk. Continuous PM2.5 exposure was associated with increased risk (OR = 1.06 per μg/m3, 95% CI: 1.05–1.08). High PM2.5 exposure (highest quartile, ≥33.294 μg/m3) combined with homozygous risk genotypes for both variants (AA/AA, cumulative score = 7) showed markedly elevated risk (OR = 6.19, 95% CI: 2.30–16.67). Sensitivity analyses confirmed consistency. Conclusion: PM2.5 exposure and genetic variants independently and cumulatively contribute to breast cancer risk, emphasizing targeted air pollution reduction among genetically vulnerable groups.