Sex-specific associations of sex hormone binding globulin and risk of bladder cancer.

IF 1.6 4区医学 Q2 MEDICINE, GENERAL & INTERNAL Open Medicine Pub Date : 2025-02-28 eCollection Date: 2025-01-01 DOI:10.1515/med-2025-1163

Junyong Ou, Hai Bi, Haobin Zhou, Zhanyi Zhang, Peichen Duan, Haoming Yin, Zezhen Zhou, Zhixin Xie, Xiaojun Tian, Jianfei Ye, Shudong Zhang

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Abstract

Background: Males have a three times higher risk of a diagnosis of bladder cancer (Bca) than females. Sex hormone-binding globulin (SHBG) may be associated with Bca risk. However, the sex-specific role of SHBG in Bca remains unclear. In this study, we aimed to determine the role of SHBG in Bca.

Methods: A sex-specific univariable Mendelian randomization (MR) analysis involving 369,426 men and 395,375 women was conducted to assess the causal relationship between SHBG and testosterone and Bca risk. Sensitivity analyses and multivariable MR were conducted to confirm the robustness of our results. Linkage disequilibrium score regression assessed the genetic correlation between these diseases influenced by heredity.

Results: Univariable MR results showed that one-SD elevated SHBG was related to a low risk of Bca in males (OR: 0.60, 95% CI: 0.39-0.93; p = 0.022) but had no benefit in females. Genetically predicted BT was positively associated with Bca risk in males (OR: 1.59; 95% CI: 1.06-2.40; p = 0.027). In multivariable MR, higher SHBG levels were not related to male Bca risk after controlling for BT.

Conclusions: Our findings do not provide evidence to support a causal relationship between SHBG and Bca risk in males although an association was observed in the univariable analysis. Further research is needed to identify the underlying pathways.

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性激素结合球蛋白与膀胱癌风险的性别特异性关联。

背景：男性患膀胱癌（Bca）的风险是女性的三倍。性激素结合球蛋白（SHBG）可能与Bca风险有关。然而，SHBG在Bca中的性别特异性作用尚不清楚。在本研究中，我们旨在确定SHBG在Bca中的作用。方法：对369426名男性和395375名女性进行了性别特异性单变量孟德尔随机化（MR）分析，以评估SHBG、睾酮和Bca风险之间的因果关系。进行敏感性分析和多变量MR来证实我们结果的稳健性。连锁不平衡评分回归评估了这些受遗传影响的疾病之间的遗传相关性。结果：单变量磁共振结果显示，1 sd的SHBG升高与男性Bca的低风险相关(OR: 0.60, 95% CI: 0.39-0.93；P = 0.022)，但对女性没有益处。基因预测BT与男性Bca风险呈正相关(OR: 1.59；95% ci: 1.06-2.40；P = 0.027)。在多变量MR中，在控制了bt后，较高的SHBG水平与男性Bca风险无关。结论：我们的研究结果并未提供证据支持SHBG与男性Bca风险之间的因果关系，尽管在单变量分析中观察到两者之间存在关联。需要进一步的研究来确定潜在的途径。

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

Open Medicine Medicine-General Medicine

CiteScore

3.00

自引率

0.00%

发文量

153

审稿时长

20 weeks

期刊介绍： Open Medicine is an open access journal that provides users with free, instant, and continued access to all content worldwide. The primary goal of the journal has always been a focus on maintaining the high quality of its published content. Its mission is to facilitate the exchange of ideas between medical science researchers from different countries. Papers connected to all fields of medicine and public health are welcomed. Open Medicine accepts submissions of research articles, reviews, case reports, letters to editor and book reviews.