Genetic Association of Primary Lung Cancer With Urological Cancers: A Bidirectional Mendelian Randomization Study and SEER Database Validation

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine Pub Date : 2025-09-29 DOI:10.1002/cam4.71272

Hao Zhou, Zihao Feng, Cunjing Zheng, Ling Xia, Ziran Dai, Zheyu Ai, Zhenwei Li, Kezhi Liu, Yinghan Wang, Ning Su, Zhenhua Chen, Jing Zhang, Xiaohan Jin

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引用次数: 0

Abstract

Background

Previous studies reported an association between lung cancer (LC) and partial urological cancers (UCs). However, the exact causal association between LC and UCs remains obscure.

Methods

A two-sample bidirectional Mendelian randomization (MR) and the Genetic Risk Scores (GRS) method were used to assess the genetic relationships between LC and UCs. The risk of second primary cancer (SPC) was validated using the Surveillance, Epidemiology, and End Results (SEER) database.

Results

MR analysis demonstrated genetic associations between overall LC and lung adenocarcinoma (LUAD) with renal cell carcinoma (RCC) (overall LC: OR [95% CI] = 1.214 [1.003–1.469], p = 0.046; LUAD: OR [95% CI] = 1.144 [1.029–1.271], p = 0.012). The GRS method also yielded consistent results (overall LC: OR [95% CI] = 1.229 [1.067–1.414], p = 0.004; LUAD: OR [95% CI] = 1.125 [1.019–1.243], p = 0.020). Therefore, this study primarily focused on the significant associations between overall LC and LUAD with RCC. Meanwhile, the SEER database was exploited to confirm the correlation between primary LUAD (PLUAD) and secondary primary RCC (SPC-RCC). The results indicated that the risk of SPC-RCC after PLUAD was substantially higher than the US reference population.

Conclusions

The MR study identified genetic associations between LC and UCs, revealing an elevated risk of SPC-RCC after primary LC (PLC), particularly LUAD. This study lays a foundation for SPC-RCC prevention after PLC, indicating the necessity of enhanced surveillance of PLC patients in clinical practice and further research into the shared biological pathways to provide innovative therapeutic alternatives.

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查看原文本刊更多论文

原发性肺癌与泌尿系统癌症的遗传关联：双向孟德尔随机研究和SEER数据库验证。

背景：以前的研究报道了肺癌（LC）和部分泌尿系统癌症（UCs）之间的关联。然而，LC和UCs之间的确切因果关系尚不清楚。方法：采用双样本双向孟德尔随机化（MR）和遗传风险评分（GRS）方法评估LC和UCs之间的遗传关系。使用监测、流行病学和最终结果（SEER）数据库验证第二原发癌（SPC）的风险。结果：MR分析显示总体LC与肺腺癌（LUAD）合并肾癌（RCC）之间存在遗传关联（总体LC: OR [95% CI] = 1.214 [1.003-1.469], p = 0.046; LUAD: OR [95% CI] = 1.144 [1.029-1.271], p = 0.012）。GRS法也得出了一致的结果（总体LC: OR [95% CI] = 1.229 [1.067-1.414], p = 0.004; LUAD: OR [95% CI] = 1.125 [1.019-1.243], p = 0.020）。因此，本研究主要关注总体LC和LUAD与RCC之间的显著关联。同时，利用SEER数据库确认主LUAD （PLUAD）与次主RCC （SPC-RCC）之间的相关性。结果表明，plad后发生SPC-RCC的风险明显高于美国参考人群。结论：MR研究确定了LC和UCs之间的遗传关联，揭示了原发性LC （PLC）后SPC-RCC的风险增加，特别是LUAD。本研究为PLC后SPC-RCC的预防奠定了基础，表明在临床实践中有必要加强PLC患者的监测，并进一步研究共享的生物学途径，以提供创新的治疗方案。

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

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.