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

Year: 2025

Type: article

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.

Source: Cancer Medicine

DOI: 10.1002/cam4.71272