Amino acids and risk of colon adenocarcinoma: a Mendelian randomization study

Abstract

Background: The existence of amino acid metabolic reprogramming in tumor cells is well established. However, the potential correlation between blood amino acids and the risk of colon adenocarcinoma remains largely unexplored. Methods: We utilized Mendelian randomization (MR) analysis to examine the association between 20 amino acids in the blood and the risk of colon adenocarcinoma. Additionally, reverse MR analysis was employed to identify the presence of reverse causality. A two-step MR analysis was conducted to ascertain the potential mediating effect. Lastly, the alanine detection data from colon adenocarcinoma patients in our hospital were utilized to investigate the differences in alanine levels among healthy individuals and patients with colon cancer, as well as among patients with different stages and locations of colon cancer. Furthermore, a Kaplan–Meier curve was employed to examine the correlation between alanine and overall survival, followed by the implementation of COX univariate analysis. Results: The results of our study indicate that there is an inverse correlation between alanine and the risk of colon adenocarcinoma. Additionally, we found no significant evidence to support a causal relationship between colon adenocarcinoma and alanine. Furthermore, our analysis revealed that alanine aminotransferase (ALT) and blood glucose do not act as mediators in this causal pathway. Moreover, individuals diagnosed with colon adenocarcinoma exhibited a significant decrease in alanine levels, particularly in cases of stage IV colon adenocarcinoma with distant metastasis. Additionally, elevated alanine levels were associated with improved overall survival rates among colon adenocarcinoma patients. Conclusions: The results of this study indicate that alanine exhibits protective characteristics against the onset of colon adenocarcinoma and may play a role in promoting a more favorable disease prognosis. Consequently, dietary interventions aimed at increasing alanine intake may serve as a potential strategy for the prevention and treatment of colon adenocarcinoma.