Li Wenhuan, Yang Yonggang, Xie Rong, Su Xinyu, Shi Pengfei, Chen Lin, Hu Bo
Department of Thyroid and Breast Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, Hubei, China.
West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
Discov Oncol. 2025 Jun 6;16(1):1019. doi: 10.1007/s12672-025-02874-9.
Air pollution has been implicated in various health conditions, including cancer. However, the relationship between long-term exposure to air pollution and breast cancer risk, its subtypes, and survival remains unclear.
This study employed a two-sample Mendelian Randomization (MR) design to investigate the causal effects of PM, PM, NO₂, and NO on breast cancer risk and survival. Genetic instruments for air pollutants were obtained from the UK Biobank, while breast cancer outcomes, were sourced from the Breast Cancer Association Consortium (BCAC) and the FinnGen study. The primary method was inverse-variance weighted (IVW), MR estimates for outcomes from various datasets were synthesized using the fixed-effects meta-analysis method. Pleiotropy and heterogeneity were evaluated with MR-Egger intercept and Cochran's Q test, while leave-one-out analysis tested the robustness of the findings.
MR analysis demonstrated a significant causal association between genetically predicted NO₂ and PM exposure and increased breast cancer risk. A one standard deviation (SD) increase in NO₂ was associated with a 68% higher risk of breast cancer, while a one SD increase in PM was linked to a 36% increased risk. Subgroup analysis revealed similar associations, particularly for both ER + and ER - subtypes with PM. In contrast, no significant associations were observed for PM or NO. Additionally, no strong evidence was found linking air pollution exposure to breast cancer survival.
This study provides evidence of a causal link between long-term exposure to NO₂ and PM and breast cancer risk, especially for hormone receptor subtypes. However, the effects of PM and NO on breast cancer risk were not significant, and air pollution exposure did not appear to impact survival. Further research is needed to elucidate the specific biological mechanisms and to extend the analysis to non-European populations.
空气污染已被认为与包括癌症在内的多种健康状况有关。然而，长期暴露于空气污染与乳腺癌风险、其亚型及生存率之间的关系仍不明确。
本研究采用两样本孟德尔随机化（MR）设计，以调查细颗粒物（PM）、可吸入颗粒物（PM）、二氧化氮（NO₂）和一氧化氮（NO）对乳腺癌风险和生存率的因果效应。空气污染物的基因工具变量来自英国生物银行，而乳腺癌结局数据则来自乳腺癌协会联盟（BCAC）和芬兰基因研究。主要方法是逆方差加权（IVW），使用固定效应荟萃分析方法综合来自各种数据集的结局的MR估计值。通过MR-Egger截距和 Cochr an's Q检验评估多效性和异质性，而留一法分析则检验研究结果的稳健性。
MR分析表明，基因预测的NO₂和PM暴露与乳腺癌风险增加之间存在显著的因果关联。NO₂每增加一个标准差（SD），患乳腺癌的风险就会增加68%，而PM每增加一个SD，风险就会增加36%。亚组分析显示了类似的关联，特别是对于PM与雌激素受体阳性（ER+）和雌激素受体阴性（ER-）亚型。相比之下，未观察到PM或NO有显著关联。此外，没有发现强有力的证据表明空气污染暴露与乳腺癌生存率有关。
本研究提供了长期暴露于NO₂和PM与乳腺癌风险之间存在因果联系的证据，特别是对于激素受体亚型。然而，PM和NO对乳腺癌风险的影响并不显著，空气污染暴露似乎也不会影响生存率。需要进一步研究以阐明具体的生物学机制，并将分析扩展到非欧洲人群。
