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已发表论文
血小板指标与乳腺癌（包括雌激素受体特异性亚型）的因果关系分析：一项孟德尔随机化研究
Received 14 May 2025
Accepted for publication 8 September 2025
Published 3 October 2025 Volume 2025:17 Pages 3455—3467
DOI https://doi.org/10.2147/IJWH.S540325
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Vinay Kumar
Yuhao Zhu,1 Jundong Wu1,2
1Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 2Shantou Key Laboratory of Precision Diagnosis and Treatment in Women’s Cancer, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China
Correspondence: Jundong Wu, Breast Center, Cancer Hospital of Shantou University Medical College, 7 Raoping Road, Shantou, Guangdong, 515041, People’s Republic of China, Tel +86-13829663428, Email wujun-dong@163.com
Background: Changes in platelet indices are associated with breast cancer. But the causal relationship between them remains unclear.
Methods: Genetic variation data of platelet indices, including platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT), were collected as instrumental variables (IVs). We assessed their impact on the risk of overall breast cancer and its estrogen receptor (ER)+ and ER- subtypes through Mendelian randomization (MR) analysis, including IVs selection, multiple corrections, causality assessment, and sensitivity analysis. Additionally, the findings were validated using an independent dataset and extended the validation to East Asian populations.
Results: Our results found that PCT was significantly associated with an increased risk of overall breast cancer (OR, 1.0693 [95% CI, 1.0281– 1.1121]; P = 0.0008) and its ER+ subtype (OR, 1.0691 [95% CI, 1.0233– 1.1169]; P = 0.0028), while they were suggestive evidence of a causal relationship after excluding the outliers determined by MR-PRESSO test. After removing the outliers, the suggestive evidence of a causal relationship between PLT and the increased risk of overall breast cancer (OR, 1.0351 [95% CI, 1.0003– 1.0711]; P = 0.0483) disappeared, whereas MPV was suggestively associated with an increased risk of overall breast cancer (P = 0.0291). PDW was suggestively associated with a lower risk of overall breast cancer (OR, 0.9597 [95% CI, 0.9236– 0.9971]; P = 0.035) and ER+ (OR, 0.9528 [95% CI, 0.9118– 0.9957]; P = 0.0315), ER- (OR, 0.9199 [95% CI, 0.8644– 0.979]; P = 0.0085) subtypes, whose outlier-corrected results were consistent with raw causal estimates. These findings were replicated in an independent dataset but did not generalize to the East Asian population.
Conclusion: This study reveals suggestive evidence of a causal relationship between platelet indices, specifically PCT, MPV, and PDW, and the risk of breast cancer and its subtypes.
Keywords: Mendelian randomization, platelet indices, breast cancer, subtypes, causal relationship
1Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 2Shantou Key Laboratory of Precision Diagnosis and Treatment in Women’s Cancer, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China
Correspondence: Jundong Wu, Breast Center, Cancer Hospital of Shantou University Medical College, 7 Raoping Road, Shantou, Guangdong, 515041, People’s Republic of China, Tel +86-13829663428, Email wujun-dong@163.com
Background: Changes in platelet indices are associated with breast cancer. But the causal relationship between them remains unclear.
Methods: Genetic variation data of platelet indices, including platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT), were collected as instrumental variables (IVs). We assessed their impact on the risk of overall breast cancer and its estrogen receptor (ER)+ and ER- subtypes through Mendelian randomization (MR) analysis, including IVs selection, multiple corrections, causality assessment, and sensitivity analysis. Additionally, the findings were validated using an independent dataset and extended the validation to East Asian populations.
Results: Our results found that PCT was significantly associated with an increased risk of overall breast cancer (OR, 1.0693 [95% CI, 1.0281– 1.1121]; P = 0.0008) and its ER+ subtype (OR, 1.0691 [95% CI, 1.0233– 1.1169]; P = 0.0028), while they were suggestive evidence of a causal relationship after excluding the outliers determined by MR-PRESSO test. After removing the outliers, the suggestive evidence of a causal relationship between PLT and the increased risk of overall breast cancer (OR, 1.0351 [95% CI, 1.0003– 1.0711]; P = 0.0483) disappeared, whereas MPV was suggestively associated with an increased risk of overall breast cancer (P = 0.0291). PDW was suggestively associated with a lower risk of overall breast cancer (OR, 0.9597 [95% CI, 0.9236– 0.9971]; P = 0.035) and ER+ (OR, 0.9528 [95% CI, 0.9118– 0.9957]; P = 0.0315), ER- (OR, 0.9199 [95% CI, 0.8644– 0.979]; P = 0.0085) subtypes, whose outlier-corrected results were consistent with raw causal estimates. These findings were replicated in an independent dataset but did not generalize to the East Asian population.
Conclusion: This study reveals suggestive evidence of a causal relationship between platelet indices, specifically PCT, MPV, and PDW, and the risk of breast cancer and its subtypes.
Keywords: Mendelian randomization, platelet indices, breast cancer, subtypes, causal relationship