Journal Article

C-reactive protein and cancer risk: a pan-cancer study of prospective cohort and Mendelian randomization analysis

Ma, Zhimin, Shen, Hongbing, Zhu, Meng, Zhang, Xu, Xu, Lin, Yin, Rong, Hang, Dong, Feng, Jifeng

2022

Overview

Background Although observational studies have reported associations between serum C-reactive protein (CRP) concentration and risks of lung, breast, and colorectal cancer, inconsistent or absent evidences were showed for other cancers. We conducted a pan-cancer analysis to comprehensively assess the role of CRP, including linearity and non-linearity associations. Methods We analyzed 420,964 cancer-free participants from UK Biobank cohort. Multivariable-adjusted Cox proportional hazards model was conducted to evaluate the observed correlation of CRP with overall cancer and 21 site-specific cancer risks. Furthermore, we performed linear and non-linear Mendelian randomization analyses to explore the potential causal relation between them. Results During a median follow-up period of 7.1 years (interquartile range: 6.3, 7.7), 34,979 incident cancer cases were observed. Observational analyses showed higher CRP concentration was associated with increased risk of overall cancer (hazard ratio (HR) = 1.02, 95% CI: 1.01, 1.02 per 1mg/L increase, P < 0.001). There was a non-linear association between CRP and overall cancer risk with inflection point at 3mg/L (false-discovery rate adjust (FDR-adjusted) P overall < 0.001 and FDR-adjusted P non-linear < 0.001). For site-specific cancer, we observed positive linear associations for cancers of esophagus and stomach (FDR-adjusted P overall < 0.050 and FDR-adjusted P non-linear > 0.050). In addition, we also observed three different patterns of non-linear associations, including “fast-to-low increase” (head and neck, colorectal, liver, lung, kidney cancer, and non-Hodgkin lymphoma), “increase-to-decrease” (breast cancer), and “decrease-to-platform” (chronic lymphocytic leukemia). Furthermore, the inflection points of non-linear association patterns were consistently at around 3mg/L. By contrast, there was no evidence for linear or non-linear associations between genetically predicted CRP and risks of overall cancer or site-specific cancers. Conclusions Our results indicated that CRP was a potential biomarker to assess risks of overall cancer and 12 site-specific cancers, while no association were observed for genetically-predicted CRP and cancer risks.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Biobanks / Biomarkers / Biomedicine / Breast cancer / Breast Neoplasms / C-reactive protein / C-Reactive Protein - genetics / C-Reactive Protein - metabolism / Cancer / Cancer risk / Chronic lymphocytic leukemia / Cohort analysis / Cohort study / Colorectal cancer / Colorectal carcinoma / Esophagus / Female / Health aspects / Health risks / Hormone replacement therapy / Humans / Inflection points / Kidney cancer / Leukemia / Liver cancer / Lung cancer / Lungs / Lymphoma / Measurement / Medicine / Medicine & Public Health / Mendelian Randomization Analysis / Neoplasms - genetics / Neoplasms - metabolism / Non-Hodgkin's lymphoma / Non-linear Mendelian randomization / Observational studies / Prospective Studies / Proteins / Quality control / Questionnaires / Randomization / Research Article / Risk / Risk assessment / Risk factors / Sensitivity analysis / Statistical models