Appraising non-linear association between pre-diagnostic platelet counts and cancer survival outcomes: observational and genetic analysis
Changtao Li,
Junhua Chen,
Deqian Han,
Chi Shu,
Jun Huang,
Linru Wei,
Haoran Luo,
Qingbin Wu,
Xin Chen,
Yazhou He,
Yanhong Zhou
Affiliations
Changtao Li
Department of Oncology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
Junhua Chen
Department of General Surgery, West China Second Hospital, Sichuan University, Chengdu, China
Deqian Han
Department of Oncology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
Chi Shu
Division of vascular surgery, Department of general surgery, West China Hospital, Sichuan University, Chengdu, China
Jun Huang
Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
Linru Wei
Department of Oncology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
Haoran Luo
Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, College of the Environment and Ecology, Xiamen University, Xiamen, Fujian, China
Qingbin Wu
Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
Xin Chen
Department of Oncology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
Yazhou He
Department of Oncology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
Yanhong Zhou
Department of laboratory medicine, West China Hospital, Sichuan University, Chengdu, China
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.
