Causal relationship between albumin, total protein, and colorectal cancer risk: A 2-sample Mendelian randomization study

Albumin (ALB) and total protein (TP) are vital constituents of the blood, and their levels and roles in the risk of colorectal cancer (CRC) are of significance. Previous observational studies have reported correlations among ALB, TP, and CRC. However, the existence of a causal relationship between ALB and CRC in European populations has not been adequately investigated and the causal link between TP and CRC remains unexplored. To address these gaps, we applied Mendelian randomization (MR) to investigate the potential causal relationship between ALB, TP, and CRC. Two-sample MR analysis was used to investigate whether there was a causal relationship between ALB, TP, and CRC. Our exposure data were extracted from genome-wide association study (GWAS) databases sourced from the UK Biobank, containing 315,268 and 314,921 Europeans participants for ALB and TP analyses, respectively. Single nucleotide polymorphisms that were significantly associated with ALB and TP were assessed using GWAS datasets. Our data were derived from the FinnGen Consortium CRC GWAS, which contained 6509 CRC cases and 28,7137 controls. Causal inference between ALB, TP, and CRC was performed using 3 MR methods: inverse variance weighting (IVW), MR-Egger, and weighted median. The IVW analysis showed no significant causal association between ALB and CRC (OR = 1.04, 95% CI = 0.89-1.21, P = .65). In contrast, the IVW analysis for TP and CRC showed a significant causal association (OR = 0.78, 95% CI = 0.66-0.92, P = .003), suggesting a reduced risk of CRC. Through a 2-sample MR study investigating the causal relationship between ALB, TP, and CRC in a European population, our findings revealed a significant causal relationship between TP and a reduced risk of CRC.