Causal associations among albumin, C-reactive protein, body mass index, and the risk of colorectal cancer

A Mendelian randomization model analysis was employed to investigate the causal direction between CRP (C-reactive protein), Alb(albumin), and BMI(body mass index), as well as their impact on colorectal cancer (CRC) risk and postoperative prognosis. Two-sample Mendelian randomization (MR) was conducted, with BMI set as the exposure variable and CRP, Alb, and CRC as the outcome variables, to determine if CRP and Alb mediate the causal relationship between BMI and CRC. Additionally, this relationship was examined using individual-level data from a retrospective cohort analysis of local cases, which included 374 incident cases of CRC. The analysis of the mediating effect of Alb on BMI and CRC risk demonstrated that in European and East Asian populations, BMI had a promoting effect on CRC risk (OR: 1.1903 and 1.3243, p < 0.05). A positive causal relationship was observed between BMI and Alb, but the effect was opposite (OR: 0.8671 and 0.9283, p < 0.05). Alb exhibited a protective effect against CRC (OR: 0.8707 and 0.7157, p < 0.05). The mediating effect of CRP indicated that BMI in European and East Asian populations was associated with an increased risk of CRC (OR: 1.0013 and 1.3243, p < 0.05). BMI and CRP had a positive causal relationship, with consistent effects (OR: 1.4306 and 1.1008, p < 0.05). CRP had a weak, albeit unclear, protective effect on CRC risk (OR: European, 0.9985; p < 0.05, and East Asian, 0.9992; p > 0.05). Relative to the MR results, a high BMI and Alb, along with a low CRP, were observed to be associated with more prolonged overall survival (OS) in the retrospective cohort univariate analysis (HR: 0.89, 0.92, and 1.02, P < 0.05). After adjusting for Alb, the association between BMI and CRC overall survival remained significant (HR: 0.91, P < 0.05). However, upon adjustment for CRP, BMI was not found to be independently associated with overall survival in patients with CRC. The findings of this study support that BMI and related factors have a causal association with the risk of colorectal cancer.