| アブストラクト | BACKGROUND: Women with autoimmune diseases (AIDs) experience chronic immune dysregulation and hormonal fluctuations, both of which may influence breast cancer risk. However, it remains unclear whether this risk is driven mainly by its treatment or the underlying disease, highlighting the need for integrating real-world data and genetic evidence. METHODS: The FDA Adverse Event Reporting System (FAERS) were utilized to identify breast cancer safety signals among women with AIDs, analyzing 11,479 reports from 2004 to 2024. Disproportionality analyses using Reporting Odds Ratio (ROR) and Information Component (IC) were conducted. Then, we mapped these drugs to their target genes and performed mendelian randomization (MR) to assess their causal relationships with breast cancer. Finally, we investigated shared genetic architecture between breast cancer and AIDs using global and local genetic correlation, cross-trait meta-analysis, and transcriptome-wide association studies. RESULTS: We identified 13 immunosuppressive drugs (TNF inhibitors, interleukin inhibitors, and monoclonal antibodies), 3 immunostimulants and 16 adjunctive drugs associated with increased breast cancer reporting in patients with AIDs. The drugs with the highest case reports for positive disproportionality analysis were interferon beta-1a (N: 1731, IC [IC025] 1.56 [1.49]), natalizumab (798, 0.65 [0.54]), and infliximab (741, 0.64 [0.53]). MR results revealed causal links between 9 drug targets and breast cancer risk, such as FDPS (OR: 0.66, p: 1.33E-08), CALCRL (OR: 0.887, p: 4.77E-06) and PARP1 (OR: 1.051, p: 3.50E-06). Global genetic correlation identified significant shared heritability between breast cancer and 3 specific AIDs, including type 1 diabetes mellitus (rg: -0.242, p: 0.95E-4), ulcerative colitis (rg: 0.125, p: 0.29E-2), and migraine (rg: 0.078, p: 0.79E-2). Specifically, the most notable genetic overlap was observed between breast cancer and type 1 diabetes mellitus, with significant shared risk SNPs (rs12046289 and rs6679677) and susceptibility genes (ADCY3 and CENPO). CONCLUSIONS: Our study uncovered several immune-related drugs associated with increased breast cancer reporting in women with AIDs. This risk may be explained by several potential drug targets with causal roles, or by the shared genetic comorbidity between specific AIDs and breast cancer. These insights emphasize the need for tailored breast cancer surveillance and highlight potential molecular targets for intervention in vulnerable populations. |
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| ジャーナル名 | Journal of translational medicine |
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| Pubmed追加日 | 2025/11/22 |
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| 投稿者 | Song, Ningning; Xi, Xinquan; Zhang, Kejian; Li, Zeyu; Kuan, Yang; Pei, Chongzhe |
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| 組織名 | Department of Breast Surgery, Department of General Surgery, The First Affiliated;Hospital of Anhui Medical University, 218 Jixi Road, Shushan District, Hefei,;Anhui, 230022, People's Republic of China. sonini00@163.com.;Anhui, 230022, People's Republic of China.;The First Clinical Medical College, New Medical Science Center of Anhui Medical;University, Hangbu River Avenue, Hefei, Anhui, 230022, People's Republic of;China.;Department of Cardiology, Tianjin Medical University General Hospital, 154 Anshan;Road, Heping District, Tianjin, 300052, People's Republic of China. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/41272700/ |
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