Appraising non-linear association between pre-diagnostic platelet counts and cancer survival outcomes: observational and genetic analysis
Previous studies have reported inconsistent associations between platelet count (PLT) and cancer survival. However, whether there is linear causal effect merits in-depth investigations. We conducted a cohort study using the UK Biobank and a two-sample Mendelian randomization (MR) analysis. PLT level...
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Taylor & Francis Group
2024-12-01
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| Series: | Platelets |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/09537104.2024.2379815 |
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| author | Changtao Li Junhua Chen Deqian Han Chi Shu Jun Huang Linru Wei Haoran Luo Qingbin Wu Xin Chen Yazhou He Yanhong Zhou |
| author_facet | Changtao Li Junhua Chen Deqian Han Chi Shu Jun Huang Linru Wei Haoran Luo Qingbin Wu Xin Chen Yazhou He Yanhong Zhou |
| author_sort | Changtao Li |
| collection | DOAJ |
| description | Previous studies have reported inconsistent associations between platelet count (PLT) and cancer survival. However, whether there is linear causal effect merits in-depth investigations. We conducted a cohort study using the UK Biobank and a two-sample Mendelian randomization (MR) analysis. PLT levels were measured prior to cancer diagnosis. We adopted overall survival (OS) as the primary outcome. Cox models were utilized to estimate the effects of PLTs on survival outcomes at multiple lag times for cancer diagnosis. We employed 34 genetic variants as PLT proxies for MR analysis. Linear and non-linear effects were modeled. Prognostic effects of gene expression harboring the instrumental variants were also investigated. A total of 65 471 cancer patients were included. We identified a significant association between elevated PLTs (per 100 × 109/L) and inferior OS (HR: 1.07; 95% CI: 1.04–1.10; p < .001). Similar significant associations were observed for several cancer types. We further observed a U-shaped relationship between PLTs and cancer survival (p < .001). Our MR analysis found null evidence to support a causal association between PLTs and overall cancer survival (HR: 1.000; 95% CI: 0.998–1.001; p = .678), although non-linear MR analysis unveiled a potential greater detrimental effect at lower PLT range. Expression of eleven PLT-related genes were associated with cancer survival. Early detection of escalated PLTs indicated possible occult cancer development and inferior subsequent survival outcomes. The observed associations could potentially be non-linear. However, PLT is less likely to be a promising therapeutic target. |
| format | Article |
| id | doaj-art-be97d8ae67aa4395b6f1a85d76a63551 |
| institution | OA Journals |
| issn | 0953-7104 1369-1635 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Platelets |
| spelling | doaj-art-be97d8ae67aa4395b6f1a85d76a635512025-08-20T02:12:19ZengTaylor & Francis GroupPlatelets0953-71041369-16352024-12-0135110.1080/09537104.2024.2379815Appraising non-linear association between pre-diagnostic platelet counts and cancer survival outcomes: observational and genetic analysisChangtao Li0Junhua Chen1Deqian Han2Chi Shu3Jun Huang4Linru Wei5Haoran Luo6Qingbin Wu7Xin Chen8Yazhou He9Yanhong Zhou10Department of Oncology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, ChinaDepartment of General Surgery, West China Second Hospital, Sichuan University, Chengdu, ChinaDepartment of Oncology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, ChinaDivision of vascular surgery, Department of general surgery, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of General Surgery, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Oncology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, ChinaKey Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, College of the Environment and Ecology, Xiamen University, Xiamen, Fujian, ChinaDepartment of General Surgery, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Oncology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, ChinaDepartment of Oncology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, ChinaDepartment of laboratory medicine, West China Hospital, Sichuan University, Chengdu, ChinaPrevious studies have reported inconsistent associations between platelet count (PLT) and cancer survival. However, whether there is linear causal effect merits in-depth investigations. We conducted a cohort study using the UK Biobank and a two-sample Mendelian randomization (MR) analysis. PLT levels were measured prior to cancer diagnosis. We adopted overall survival (OS) as the primary outcome. Cox models were utilized to estimate the effects of PLTs on survival outcomes at multiple lag times for cancer diagnosis. We employed 34 genetic variants as PLT proxies for MR analysis. Linear and non-linear effects were modeled. Prognostic effects of gene expression harboring the instrumental variants were also investigated. A total of 65 471 cancer patients were included. We identified a significant association between elevated PLTs (per 100 × 109/L) and inferior OS (HR: 1.07; 95% CI: 1.04–1.10; p < .001). Similar significant associations were observed for several cancer types. We further observed a U-shaped relationship between PLTs and cancer survival (p < .001). Our MR analysis found null evidence to support a causal association between PLTs and overall cancer survival (HR: 1.000; 95% CI: 0.998–1.001; p = .678), although non-linear MR analysis unveiled a potential greater detrimental effect at lower PLT range. Expression of eleven PLT-related genes were associated with cancer survival. Early detection of escalated PLTs indicated possible occult cancer development and inferior subsequent survival outcomes. The observed associations could potentially be non-linear. However, PLT is less likely to be a promising therapeutic target.https://www.tandfonline.com/doi/10.1080/09537104.2024.2379815Cancer survivalcohort studyMendelian randomizationplatelet counts |
| spellingShingle | Changtao Li Junhua Chen Deqian Han Chi Shu Jun Huang Linru Wei Haoran Luo Qingbin Wu Xin Chen Yazhou He Yanhong Zhou Appraising non-linear association between pre-diagnostic platelet counts and cancer survival outcomes: observational and genetic analysis Platelets Cancer survival cohort study Mendelian randomization platelet counts |
| title | Appraising non-linear association between pre-diagnostic platelet counts and cancer survival outcomes: observational and genetic analysis |
| title_full | Appraising non-linear association between pre-diagnostic platelet counts and cancer survival outcomes: observational and genetic analysis |
| title_fullStr | Appraising non-linear association between pre-diagnostic platelet counts and cancer survival outcomes: observational and genetic analysis |
| title_full_unstemmed | Appraising non-linear association between pre-diagnostic platelet counts and cancer survival outcomes: observational and genetic analysis |
| title_short | Appraising non-linear association between pre-diagnostic platelet counts and cancer survival outcomes: observational and genetic analysis |
| title_sort | appraising non linear association between pre diagnostic platelet counts and cancer survival outcomes observational and genetic analysis |
| topic | Cancer survival cohort study Mendelian randomization platelet counts |
| url | https://www.tandfonline.com/doi/10.1080/09537104.2024.2379815 |
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