Association between serum urate levels, gout and breast cancer: observational and Mendelian randomization analyses.

IF 1.5 4区医学 Q4 ONCOLOGY

Translational cancer research Pub Date : 2025-01-31 Epub Date: 2025-01-20 DOI:10.21037/tcr-24-1141

Shuai Wang, Zhiyuan Zhang, Yuqing Su, Shoukai Wang, Wenwen Li, Qi Liu, Pilei Si, Wentao Li

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引用次数: 0

Abstract

Background: It is hypothesized that uric acid acts as an antioxidant and may prevent cancer. However, observational studies regarding the relationship between serum urate levels, gout, and breast cancer have provided discrepant evidence. Therefore, the objective of our study was to investigate the potential causal relationship between them.

Methods: This study included 12,451 participants from the National Health and Nutrition Examination Survey (NHANES) 2009-2018. Associations between urate levels, gout, and breast cancer were examined using multivariate logistic regression analysis. In addition, to assess the causal link among them, Mendelian randomization (MR) analysis was conducted, primarily using the inverse variance weighted (IVW) approach, supplemented by MR Egger and weighted median approaches, and a set of sensitivity analyses to test the robustness of the results, and finally, multivariate MR was used to adjust for confounders.

Results: In cross-sectional studies, urate levels [odds ratio (OR) 0.99, 95% confidence interval (CI): 0.89-1.09, P=0.80] and gout (OR 0.96, 95% CI: 0.53-1.76, P=0.90) were negatively associated with breast cancer risk after controlling for multiple confounders, although the P value was not significant. Two-sample MR analysis showed that serum urate levels were negatively associated with the estrogen receptor-negative (ER-) breast cancer (IVW, OR 0.916, 95% CI: 0.848-0.989, P=0.03) risk, but not significantly associated with overall and the estrogen receptor-positive (ER+) breast cancer (IVW, both P>0.05). In addition, gout was negatively associated with overall (IVW, OR 0.07, 95% CI: 0.008-0.594, P=0.02), ER+ (IVW, OR 0.062, 95% CI: 0.005-0.742, P=0.03), and ER- breast cancer (IVW, OR 0.041, 95% CI: 0.004-0.472, P=0.01) risk. These associations persisted after multivariate MR adjustment for smoking status, alcohol intake frequency, and body mass index (BMI).

Conclusions: Our study elucidated the relationship between uric acid, gout and breast cancer, and further studies are still needed in the future to clarify the mechanisms involved.

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血清尿酸水平、痛风和乳腺癌之间的关系：观察性和孟德尔随机分析。

背景：尿酸被认为是一种抗氧化剂，可以预防癌症。然而，关于血清尿酸水平、痛风和乳腺癌之间关系的观察性研究提供了不同的证据。因此，本研究的目的是探讨两者之间潜在的因果关系。方法：本研究纳入了2009-2018年国家健康与营养检查调查（NHANES）的12451名参与者。尿酸水平、痛风和乳腺癌之间的关系采用多变量logistic回归分析。此外，为了评估它们之间的因果关系，我们进行了孟德尔随机化（MR）分析，主要采用逆方差加权（IVW）方法，辅以MR Egger和加权中位数方法，并进行了一组敏感性分析来检验结果的稳健性，最后使用多变量MR来调整混杂因素。结果：在横断面研究中，在控制多个混杂因素后，尿酸水平[比值比（OR） 0.99, 95%可信区间（CI）： 0.89-1.09， P=0.80]和痛风（OR 0.96, 95% CI: 0.53-1.76， P=0.90）与乳腺癌风险呈负相关，尽管P值不显著。两样本MR分析显示，血清尿酸水平与雌激素受体阴性（ER-）乳腺癌（IVW, OR 0.916, 95% CI: 0.848-0.989， P=0.03）风险呈负相关，但与总体和雌激素受体阳性（ER+）乳腺癌（IVW， P均为0.05）无显著相关性。此外，痛风与总体（IVW, OR 0.07, 95% CI: 0.008-0.594， P=0.02）、ER+ （IVW, OR 0.062, 95% CI: 0.005-0.742， P=0.03）和ER-乳腺癌（IVW, OR 0.041, 95% CI: 0.004-0.472， P=0.01）风险呈负相关。在对吸烟状况、饮酒频率和体重指数（BMI）进行多变量磁共振校正后，这些关联仍然存在。结论：我们的研究阐明了尿酸、痛风和乳腺癌之间的关系，未来还需要进一步的研究来阐明其中的机制。

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.