111614
论文已发表
注册即可获取德孚的最新动态
IF 收录期刊
- 3.4 Breast Cancer (Dove Med Press)
- 3.2 Clin Epidemiol
- 2.6 Cancer Manag Res
- 2.9 Infect Drug Resist
- 3.7 Clin Interv Aging
- 5.1 Drug Des Dev Ther
- 3.1 Int J Chronic Obstr
- 6.6 Int J Nanomed
- 2.6 Int J Women's Health
- 2.9 Neuropsych Dis Treat
- 2.8 OncoTargets Ther
- 2.0 Patient Prefer Adher
- 2.2 Ther Clin Risk Manag
- 2.5 J Pain Res
- 3.0 Diabet Metab Synd Ob
- 3.2 Psychol Res Behav Ma
- 3.4 Nat Sci Sleep
- 1.8 Pharmgenomics Pers Med
- 2.0 Risk Manag Healthc Policy
- 4.1 J Inflamm Res
- 2.0 Int J Gen Med
- 3.4 J Hepatocell Carcinoma
- 3.0 J Asthma Allergy
- 2.2 Clin Cosmet Investig Dermatol
- 2.4 J Multidiscip Healthc
已发表论文
常见镇痛药对乳腺癌风险及生存结局的差异因果效应：基于孟德尔随机化的证据
Received 27 June 2025
Accepted for publication 10 November 2025
Published 9 December 2025 Volume 2025:17 Pages 5287—5301
DOI https://doi.org/10.2147/IJWH.S550159
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Elie Al-Chaer
Zhan Peng,* Zhuobin Liu, Guangye Wang*
Department of Spinal Surgery, Shenzhen Baoan District People’s Hospital, the Second Affiliated Hospital of Shenzhen University, Shenzhen, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Zhan Peng, Department of Spinal Surgery, Shenzhen Baoan District People’s Hospital, No. 118, Longjing Two Road, Xinan Street, Shenzhen, 518101, People’s Republic of China, Email 819567092@qq.com Guangye Wang, Department of Spinal Surgery, Shenzhen Baoan District People’s Hospital, No. 118, Longjing Two Road, Xinan Street, Shenzhen, 518101, People’s Republic of China, Email szbayyjzwk2018@163.com
Background: The causal effects of widely used analgesics—paracetamol(acetaminophen), aspirin (acetylsalicylic acid), and ibuprofen—on breast cancer risk and survival remain uncertain. This Mendelian randomization (MR) study investigated their causal relationships with breast cancer incidence, mortality, and estrogen receptor (ER)-subtype heterogeneity.
Methods: Using two-sample MR, genetic instruments for analgesic use were derived from UK Biobank GWAS (N=457,547). Outcome data included breast cancer incidence (122,977 cases/105,974 controls), ER-subtypes (ER+: 69,501 cases; ER−: 21,468 cases), and survival statistics. Inverse-variance weighted (IVW) analyses were primary, supplemented by MR-Egger, weighted median/mode, and sensitivity analyses (MR-PRESSO, leave-one-out). Bidirectional MR assessed reverse causation.
Results: Genetically predicted paracetamol use increased overall breast cancer risk (IVW OR=3.26, 95% CI:1.60– 6.63, pFDR=0.005) and ER+ subtype risk (OR=3.65, 1.79– 7.45, pFDR=0.003). Aspirin use showed no association with incidence but improved overall survival (HR=0.0036, 0.0001– 0.1218, pFDR=0.016). Ibuprofen demonstrated no significant associations with risk or survival. Subtype-specific survival analyses were null. No reverse causation was detected (all p > 0.05). Sensitivity analyses confirmed robustness, with minimal pleiotropy (MR-Egger intercept p > 0.05) and consistent effects after outlier correction.
Conclusion: This MR study links a genetic predisposition to paracetamol use with increased breast cancer risk (especially ER+), and to aspirin use with improved survival. These divergent findings point to drug-specific mechanisms, warranting caution with long-term paracetamol use and further study of aspirin’s therapeutic potential. Clinical decisions should balance analgesic benefits against these potential cancer-related outcomes.
Keywords: breast cancer, paracetamol, aspirin, ibuprofen, Mendelian randomization, nonsteroidal anti-inflammatory drugs, pharmacoepidemiology
Department of Spinal Surgery, Shenzhen Baoan District People’s Hospital, the Second Affiliated Hospital of Shenzhen University, Shenzhen, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Zhan Peng, Department of Spinal Surgery, Shenzhen Baoan District People’s Hospital, No. 118, Longjing Two Road, Xinan Street, Shenzhen, 518101, People’s Republic of China, Email 819567092@qq.com Guangye Wang, Department of Spinal Surgery, Shenzhen Baoan District People’s Hospital, No. 118, Longjing Two Road, Xinan Street, Shenzhen, 518101, People’s Republic of China, Email szbayyjzwk2018@163.com
Background: The causal effects of widely used analgesics—paracetamol(acetaminophen), aspirin (acetylsalicylic acid), and ibuprofen—on breast cancer risk and survival remain uncertain. This Mendelian randomization (MR) study investigated their causal relationships with breast cancer incidence, mortality, and estrogen receptor (ER)-subtype heterogeneity.
Methods: Using two-sample MR, genetic instruments for analgesic use were derived from UK Biobank GWAS (N=457,547). Outcome data included breast cancer incidence (122,977 cases/105,974 controls), ER-subtypes (ER+: 69,501 cases; ER−: 21,468 cases), and survival statistics. Inverse-variance weighted (IVW) analyses were primary, supplemented by MR-Egger, weighted median/mode, and sensitivity analyses (MR-PRESSO, leave-one-out). Bidirectional MR assessed reverse causation.
Results: Genetically predicted paracetamol use increased overall breast cancer risk (IVW OR=3.26, 95% CI:1.60– 6.63, pFDR=0.005) and ER+ subtype risk (OR=3.65, 1.79– 7.45, pFDR=0.003). Aspirin use showed no association with incidence but improved overall survival (HR=0.0036, 0.0001– 0.1218, pFDR=0.016). Ibuprofen demonstrated no significant associations with risk or survival. Subtype-specific survival analyses were null. No reverse causation was detected (all p > 0.05). Sensitivity analyses confirmed robustness, with minimal pleiotropy (MR-Egger intercept p > 0.05) and consistent effects after outlier correction.
Conclusion: This MR study links a genetic predisposition to paracetamol use with increased breast cancer risk (especially ER+), and to aspirin use with improved survival. These divergent findings point to drug-specific mechanisms, warranting caution with long-term paracetamol use and further study of aspirin’s therapeutic potential. Clinical decisions should balance analgesic benefits against these potential cancer-related outcomes.
Keywords: breast cancer, paracetamol, aspirin, ibuprofen, Mendelian randomization, nonsteroidal anti-inflammatory drugs, pharmacoepidemiology