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Testosterone and colorectal cancer: a bidirectional Mendelian randomization study.
Junxing Li1, Xinmei Yan1, Huyu Jiao1
1Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Translational Cancer Research
|February 20, 2025
Summary
Bioavailable testosterone (BT) causally increases colorectal cancer (CRC) risk, while total testosterone (TT) shows no link. This study clarifies the testosterone-colorectal cancer relationship using robust Mendelian randomization methods.
Area of Science:
- Endocrinology
- Oncology
- Genetic Epidemiology
Background:
- Mendelian randomization (MR) studies on testosterone and colorectal cancer (CRC) have yielded controversial results.
- Previous research lacked sufficient sample size and stringent methods to exclude confounding factors.
Purpose of the Study:
- To investigate the genetically determined relationship between total testosterone (TT) and bioavailable testosterone (BT) with CRC.
- To clarify the causal links using a large sample size and advanced MR techniques.
Main Methods:
- Utilized bidirectional two-sample MR analysis on genome-wide association studies (GWAS) data.
- Employed inverse variance weighting (IVW), MR-Egger, and weighted median methods for causal inference.
- Conducted sensitivity analyses to ensure the robustness of findings.
Main Results:
- A one SD increase in genetically predicted BT was associated with increased CRC risk (OR=1.834, P=0.02).
- No significant causal relationship was observed between CRC and BT, nor between CRC and TT.
- Bidirectional analysis indicated CRC does not causally affect BT levels.
Conclusions:
- Bioavailable testosterone (BT) has a causal effect on colorectal cancer (CRC) risk.
- Colorectal cancer (CRC) does not appear to influence BT levels.
- Total testosterone (TT) shows no causal relationship with CRC, refining understanding of hormonal influences on cancer.
