Causal Associations of 33 Health Examination Indicators and Colorectal Cancer in European and East Asian Populations: A Mendelian Randomization Analysis.

Abstract

Background: Colorectal cancer (CRC) is a significant cause of cancer-related mortality worldwide. While many health examination indicators might be associated with CRC, their causal relationships remain unclear. The authors analyzed their causal relationship in European and East Asian populations. Methods: The authors collected the genome-wide association data for 33 clinical indicators and CRC in European and East Asian populations from the IEU OpenGWAS project and Riken's Japanese Genetic Association Database. These indicators include 13 hematological indicators, 7 liver function indicators, 2 kidney function indicators, 5 lipid metabolism indicators, 2 glucose metabolism indicators, 1 electrolyte indicator, and 3 comorbidity indicators. The authors performed univariate (UV) and multivariate (MV) Mendelian randomization (MR) analyses on the European and East Asian populations and followed a meta-analysis. Results: UVMR analysis identified 11 indicators (white blood cell count [WBC], mean corpuscular hemoglobin [MCH], mean corpuscular hemoglobin concentration, mean corpuscular volume [MCV], platelet count [Plt], C-reactive protein [CRP], total protein [TP], aspartate aminotransferase [AST], total cholesterol [TC], low-density lipoprotein cholesterol, and apolipoprotein B) with significant causal relationships (p < 0.05). Notably, AST, TC, glycated hemoglobin, and serum creatinine showed inverted causal relationships in different populations. After MV adjustment for TC and TP, MCH (odds ratio [OR]_EU = 1.0012, 1.0000 to 1.0024; OR_meta = 1.0012, 1.0001 to 1.0024), Plt (OR_EU = 0.9986, 0.9974 to 0.9998; OR_meta = 0.9986, 0.9974 to 0.9998), and CRP (OR_EU = 0.9981, 0.9965 to 0.9998; OR_meta = 0.9981, 0.9965 to 0.9998) were independent influencing indicators in European and Eurasian populations, whereas WBC (OR_EAS = 0.8316, 0.7005 to 0.9871), MCH (OR_EAS = 1.2430, 1.1132 to 1.3879), and MCV (OR_EAS = 1.0012, 1.0001 to 1.0024) were independent influencing indicators in the East Asian population. Conclusion: The causal relationship between MCH, TP, and Plt and CRC has been discovered for the first time. Furthermore, TC and CRP were also independent influencing indicators. These findings offer beneficial referential value for the enhancement of preliminary screening protocols for CRC.