ArticleInternational journal of women's health2026
Global Burden of Secondhand Smoke-Attributable ER-Negative Breast Cancer and Exploratory Immune-Metabolic Mediation Using Mendelian Randomization.
Article in International journal of women's health, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: The global burden of breast cancer attributable to secondhand smoke (SHS) and its potential biological pathways, particularly for estrogen receptor (ER)-negative disease, remain incompletely characterized. This study aimed to evaluate temporal trends in SHS-attributable breast cancer burden and to explore whether immune and metabolic traits may represent candidate pathways linking SHS exposure with ER-negative breast cancer. Methods: We analyzed the Global Burden of Disease 1990-2021 data to estimate temporal trends in SHS-attributable breast cancer burden using Joinpoint regression, Bayesian age-period-cohort modeling, decomposition analysis, and autoregressive integrated moving average forecasting to 2050. Two-sample Mendelian randomization (MR) was performed using 36-38 single-nucleotide polymorphism instruments for exposure to tobacco smoke outside the home. Exploratory two-step MR mediation analyses screened 637 serum metabolites and 731 immune phenotypes using the product-of-coefficients approach. Results: Globally, absolute SHS-attributable breast cancer deaths increased from 4,949 in 1990 to 7,518 in 2021, and disability-adjusted life years (DALYs) increased from 1.74×10 Conclusion: The age-standardized burden of SHS-attributable breast cancer has declined globally, whereas absolute deaths and DALYs have increased due to demographic growth and aging, with persistent SDI-linked disparities. MR analyses provided suggestive genetic-instrument evidence linking SHS exposure outside the home with ER-negative breast cancer, and exploratory mediation analyses prioritized lipid metabolism, ketone-related energy pathways, and myeloid immune phenotypes for future validation. These findings support continued smoke-free policies and highlight the need for larger, diverse, and mechanistically informed studies to validate the potential immune-metabolic pathways implicated in SHS-related ER-negative breast cancer.
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