Clinical and Translational Research
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. May 15, 2024; 16(5): 1995-2005
Published online May 15, 2024. doi: 10.4251/wjgo.v16.i5.1995
Casual associations between blood metabolites and colon cancer
Ke-Yue Hu, Yi-Quan Cheng, Zhi-Long Shi, Fu-Peng Ren, Gang-Feng Xiao
Ke-Yue Hu, Yi-Quan Cheng, Zhi-Long Shi, Fu-Peng Ren, Gang-Feng Xiao, Department of Hematology and Oncology, Ningbo No. 2 Hospital, Ningbo 315000, Zhejiang Province, China
Author contributions: Hu KY and Chen YQ contributed equally to this work; Hu KY and Chen YQ designed the research study; Shi ZL performed the research; Ren FQ contributed new reagents and analytic tools; Xiao GF analyzed the data and wrote the manuscript; All authors have read and approved the final manuscript.
Supported by the General Project of Medical and Health Technology Plan of Zhejiang Province, No. 2020KY845.
Institutional review board statement: Ethical approval was obtained from the FinnGen steering committee for all selected GWASs in the FinnGen Consortium, and individuals provided written informed consent.
Clinical trial registration statement: The study is not applicable.
Informed consent statement: Ethics approval of the protocol and data collection, and written informed consent from each participant were obtained by the original GWASs.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author at
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Gang-Feng Xiao, MD, PhD, Doctor, Department of Hematology and Oncology, Ningbo No. 2 Hospital, No. 41 Northwest Street, Haishu District, Ningbo 315000, Zhejiang Province, China.
Received: January 18, 2024
Peer-review started: January 18, 2024
First decision: January 26, 2024
Revised: February 2, 2024
Accepted: March 13, 2024
Article in press: March 13, 2024
Published online: May 15, 2024
Processing time: 111 Days and 23.8 Hours
Research background

Limited knowledge exists regarding the casual associations linking blood metabolites and the risk of developing colorectal cancer.

Research motivation

Colorectal cancer development is associated with the presence of five specific blood metabolites. These metabolites have been identified as causal agents and have been validated as risk factors for the disease.

Research objectives

To investigate causal associations between blood metabolites and colon cancer.

Research methods

The study utilized a two-sample Mendelian randomization (MR) analysis to investigate the causal impact of 486 blood metabolites on colorectal cancer. The primary method of analysis used was the inverse variance weighted (IVW) model. To further validate the results several sensitivity analyses were performed, including Cochran's Q test, MR-Egger intercept test, and Mendelian randomization robust adjusted profile score (MR-RAPS). These additional analyses were conducted to ensure the reliability and robustness of the findings.

Research results

After rigorous selection for genetic variation, 486 blood metabolites were included in the MR analysis. We found Mannose [odds ratio (OR) = 2.09 (1.10-3.97), P = 0.024], N-acetylglycine [OR = 3.14 (1.78-5.53), P =7.54 × 10-8], X-11593-O-methylascorbate [OR = 1.68 (1.04-2.72), P = 0.034], 1-arachidonoylglycerophosphocholine [OR 4.23 (2.51-7.12), P = 6.35 × 10-8] and 1- arachidonoylglycerophosphoethanolamine 4 [OR = 3.99 (1.17-13.54), P = 0.027] were positively causally associated with colorectal cancer, and we also found a negative causal relationship between Tyrosine [OR = 0.08 (0.01-0.63), P = 0.014], Urate [OR =0.25 (0.10-0.62), P = 0.003], N-acetylglycine [0.73 (0.54-0.98), P = 0.033], X-12092 [OR =0.89 (0.81-0.99), P = 0.028], Succinylcarnitine [OR =0.48 (0.27-0.84), P = 0.09] with colorectal cancer. A series of sensitivity analyses were performed to confirm the rigidity of the results.

Research conclusions

This study showed a causal relationship between 10 blood metabolites and colorectal cancer, of which 5 blood metabolites were found to be causal for the development of colorectal cancer and were confirmed as risk factors. The other five blood metabolites are protective factors.

Research perspectives

A significant inverse relationship has been observed between the remaining five blood metabolites and the development of colorectal cancer, establishing them as protective.