Hemoglobin levels in red blood cells and risk of colorectal cancer: A causal investigation based on Mendelian randomization

Mean corpuscular hemoglobin (MCH) is a critical parameter in red blood cells, associated with various diseases. While studies suggest a potential link between MCH levels and colorectal cancer (CRC), observational studies are insufficient to establish causality directly. This study utilized a 2-sample Mendelian randomization (MR) approach to investigate the genetic causal relationship between MCH and colorectal cancer (CRC). Genome-wide association study (GWAS) summary data for both MCH and CRC were sourced from relevant databases. MR analyses were performed using methods including inverse variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode. Cochrane’s Q test was applied to assess heterogeneity in the MR findings. Horizontal pleiotropy was evaluated using the MR-Egger intercept test and the MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test. Additionally, a leave-one-out analysis was conducted to assess the robustness of this association. The IVW method demonstrated that MCH is an independent risk factor for colorectal cancer ( P = .013). Horizontal pleiotropy is unlikely to influence the causal relationship ( P > .05), and there was no evidence of heterogeneity among the genetic variants ( P > .05). Lastly, the leave-one-out test confirmed the stability and robustness of the association. All participants in the GWAS were derived from a specific population. Due to limitations inherent to the database, the Mendelian Randomization (MR) analysis was unable to incorporate stratified analyses by country, ethnicity, or age group.