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

Sep 23, 2026

Uploaded by Ben

Background: Previous studies reported an association between lung cancer (LC) and partial urological cancers (UCs), but the exact causal relationship remains unclear. Methods: Two-sample bidirectional Mendelian randomization assessed genetic relationships between LC and UCs, and genetic risk scores (GRS) supported the findings. The Surveillance, Epidemiology, and End Results (SEER) database validated second primary cancer risk. Results showed significant genetic associations, and SEER confirmed elevated risk of secondary primary RCC after primary LUAD.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusions

Introduction

Cancer Medicine | RESEARCH ARTICLE OPEN ACCESS
Genetic Association of Primary Lung Cancer With Urological Cancers: A Bidirectional Mendelian Randomization Study and SEER Database Validation
Hao Zhou1,2 | Zihao Feng2 | Cunjing Zheng3 | Ling Xia4 | Ziran Dai2 | Zheyu Ai2 | Zhenwei Li2 | Kezhi Liu2 | Yinghan Wang2 | Ning Su1 | Zhenhua Chen2 | Jing Zhang5 | Xiaohan Jin1
1State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Institute of Tuberculosis, Institute of Pulmonary Diseases, Department of Oncology, Guangzhou Chest Hospital Affiliated to Guangdong Pharmaceutical University, Guangzhou, China | 2Department of Urology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China | 3Department of Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China | 4Department of Cataract, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China | 5Department of Pulmonary
and Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China Correspondence: Jing Zhang ([zhangj265@mail.sysu.edu.cn](zhangj265@mail.sysu.edu.cn)) | Xiaohan Jin ([jinxh5@mail.sysu.edu.cn](jinxh5@mail.sysu.edu.cn))
Received: 23 December 2024 | Revised: 30 March 2025 | Accepted: 15 September 2025
Funding: This study was supported by the Natural Science Foundation of Guangdong Province, China (2023A1515030038, 2025A1515012568), the National Natural Science Foundation of China (82403606), Guangzhou Municipal Science and Technology Project, China (2025A03J3857), Key Medical Discipline of Guangzhou-Tuberculosis (2025-2027) and China Postdoctoral Science Foundation (2023M744075) .
Keywords: GRS | lung cancer | Mendelian randomization | SEER database | urological cancer | | --- | | 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 | | | | Abbreviations: BCa, bladder cancer; CI, confidence interval; EAR, excess absolute risk; GRS, genetic risk score; GWAS, genome-wide association study; InSIDE, instrument strength independent of direct effect; IVs, instrumental variables; IVW, inverse variance weighted; LC, lung cancer; LD, linkage disequilibrium; LUAD, lung adenocarcinoma; LUSC, squamous cell lung carcinoma; MP-SIR, multiple primary standardized incidence ratios; MR, Mendelian randomization; MR-PRESSO, Mendelian randomization pleiotropy residual sum and outlier; MR-RAPS, MR-robust adjusted profile score; NSCLC, non-small cell lung cancer; PCa, prostate cancer;
PLC, primary lung cancer; PLU

FAQs

What question does the study address about lung and urological cancers?

It evaluates whether there is a causal genetic association between primary lung cancer and urological cancers, and how this relates to second primary cancer risk.

How were causal genetic relationships assessed in this research?

The study used two-sample bidirectional Mendelian randomization and genetic risk score (GRS) methods to examine genetic relationships between lung cancer and urological cancers.

What role did the SEER database play?

SEER database validation was used to confirm the correlation between primary LUAD and the risk of secondary primary RCC after primary lung cancer.

Sep 23, 2026

Uploaded by Ben