Testosterone and colorectal cancer: a bidirectional Mendelian randomization study.

IF 1.7 4区医学 Q4 ONCOLOGY Translational cancer research Pub Date : 2025-01-31 Epub Date: 2025-01-17 DOI:10.21037/tcr-24-1481

Junxing Li, Xinmei Yan, Huyu Jiao, Jingjing Chen, Zhengang Zhang

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Abstract

Background: Although Mendelian randomization (MR) studies have been conducted on the causal relationship of testosterone on colorectal cancer (CRC), the result remains controversial. We aimed to explore the genetically determined relationships between total testosterone (TT) and bioavailable testosterone (BT) with CRC using a larger sample size and more stringent methods to exclude confounding factors.

Methods: Based on genome wide association studies (GWAS) data of TT, BT and CRC, we utilized bidirectional two-sample MR methods to analyze their interrelationships. Causal relationship analysis was conducted using inverse variance weighting (IVW), MR-Egger, weighted median, simple mode and weighted mode. Sensitivity analyses were performed to examine the stability of the causal relationships.

Results: The bidirectional MR analysis revealed one standard deviation (SD) increase in genetically predicted BT increased the risk of CRC [IVW: odds ratio (OR) =1.834, 95% confidence interval (CI): 1.121-3.001, P=0.02] and there was no causal relationship of CRC on BT. There was no causal relationship between CRC and TT.

Conclusions: The findings of this study revealed a causal effect of BT on the risk of CRC, and CRC may not affect BT levels. Additionally, there was no causal relationship found between CRC and TT. Our results enhance the understanding of the real causal relationship between testosterone and CRC.

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睾酮与结直肠癌：一项双向孟德尔随机研究。

背景：虽然孟德尔随机化（MR）研究已经对睾酮与结直肠癌（CRC）的因果关系进行了研究，但结果仍然存在争议。我们的目的是通过更大的样本量和更严格的方法来排除混杂因素，探索总睾酮（TT）和生物可利用睾酮（BT）与结直肠癌之间的遗传决定关系。方法：基于TT、BT和CRC的全基因组关联研究（GWAS）数据，采用双向双样本MR方法分析三者之间的相互关系。采用方差反加权（IVW）、MR-Egger、加权中位数、简单模式和加权模式进行因果关系分析。进行敏感性分析以检验因果关系的稳定性。结果：双向MR分析显示，基因预测BT增加1个标准差（SD）会增加结直肠癌的风险[IVW：比值比(OR) =1.834, 95%可信区间（CI）： 1.121-3.001， P=0.02]， BT与结直肠癌无因果关系，TT与结直肠癌无因果关系。结论：本研究结果揭示了BT与结直肠癌风险的因果关系，结直肠癌可能不影响BT水平。此外，CRC和TT之间没有因果关系。我们的结果增强了对睾酮和结直肠癌之间真正因果关系的理解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational cancer research ONCOLOGY-

CiteScore

2.10

自引率

0.00%

发文量

252

期刊介绍： Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.