Mendelian randomization analysis reveals a protective association between genetically predicted systemic lupus erythematosus and renal cell carcinoma - Observational Study

Sep 21, 2026

Uploaded by Finn

Observational studies suggest systemic lupus erythematosus (SLE) may relate to a higher risk of urological cancers, but causality remains unclear. This study used a Mendelian randomization (MR) framework to evaluate the causal effect of genetically predicted SLE on urological cancer outcomes. The primary analysis applied inverse variance weighted MR, followed by sensitivity checks including MR-Egger regression, heterogeneity testing, and leave-one-out analyses. Two-sample MR indicated a reduced risk of renal cell carcinoma (RCC) for genetically predicted SLE, while no meaningful associations were detected for bladder or prostate cancer.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages7

Reading Time18 min

AccessFree to download

Introduction

Observational background and rationale

Role of modifiable risk factors and autoimmune disease

Study focus on SLE and urological cancers

® Observational Study Mendelian randomization analysis reveals a protective association between genetically predicted systemic lupus erythematosus and renal cell carcinoma Tian An, MMa , Wenzhi Zhang, BMa ,* | Abstract
Observational studies have suggested that there may be a connection between systemic lupus erythematosus (SLE) and a higher likelihood of developing urological cancers, although the exact cause-effect relationship is still unclear. This study therefore investigated the causal relationship between SLE and urological cancers using the Mendelian randomization (MR) approach. Our primary MR analysis involved using the inverse variance weighted method, which employed an inverse-variance-weighted approach, to examine the causal relationship between SLE and urological conditions. In addition, we performed various sensitivity analyses, such as MR-Egger regression, tests for heterogeneity, and leave-one-out sensitivity tests, to assess the reliability of our results. The findings from our analysis using Two-Sample MR showed that genetically predicted SLE was linked to a reduced likelihood of developing renal cell carcinoma (RCC) (odds ratio = 0.9996, 95% confidence interval = 0.9993–0.9999, P value = .0159) . These results suggest a possible protective impact of SLE against RCC. Nevertheless, no substantial correlation was detected between SLE and the likelihood of developing bladder cancer or prostate cancer. Collectively, these findings offer significant fresh perspectives on the possible correlation between SLE and genitourinary malignancies, specifically RCC, which will provide ideas and basis for the treatment of RCC. | | --- | | Abbreviations: BCa = bladder cancer, GWAS = genome-wide association study, IVs = instrumental variables, IVW = inverse variance weighted, MR = Mendelian randomization, PCa = prostate cancer, RCC = renal cell carcinoma, RCTs = randomized controlled trials, SLE = systemic lupus erythematosus, SNPs = single nucleotide polymorphisms. | | Keywords: bladder cancer, Mendelian randomization analysis, prostate cancer, renal cell carcinoma, systemic lupus erythematosus | 1. Introduction Kidney, bladder, and prostate cancers (PCas) are the predominant types of all cancer cases in the field of urology. These tumors are especially worrisome because they present substantial dangers to human well-being.[1–3] The incidence of these cancers is mainly influenced by factors such as advancing age, family background, intake of a fatty diet and insufficient physical activity.[4] To reduce the burden of urological cancers, attention should be given to other modifiable risk factors, such as autoimmune diseases. By addressing these risk factors, we can work toward preventing the incidence of urological cancers and improving overall health outcomes. Systemic lupus erythematosus (SLE) is a condition where the immune system mistakenly attacks various organs and systems throughout the body.[5] It can trigger a range of autoimmune reactions as the immune system of SLE patients mistakenly attacks their own tissues and organs, leading to inflammation and damage. [6] The presence of inflammation is recognized as a possible factor in the progression of cancer, and there is a potential link between specific medications utilized for treating autoimmune disorders such as SLE and an elevated likelihood of developing cancer. An increased risk of cancer has been associated with cyclophosphamide, which isan alkylating agent utilized in the treatment of SLE. [7] Previous research has indicated that individuals with SLE commonly face an increased likelihood of developing particular forms of cancer in comparison to the overall populace, although the risk of specific malignancies might be diminished or remain unaltered. [8] Nevertheless, additional research is required The authors have no funding and conflicts of interest to disclose. The datasets generated during and/or analyzed during the current study are no

FAQs

What method was used to test the causal relationship between SLE and urological cancers?

The study used a Mendelian randomization (MR) approach, with an inverse variance weighted (IVW) primary analysis and additional sensitivity analyses.

What did the MR results show for renal cell carcinoma (RCC)?

Genetically predicted SLE was linked to a reduced likelihood of developing renal cell carcinoma (RCC) in the two-sample MR analysis.

Did SLE show a causal association with bladder cancer or prostate cancer?

No substantial correlation was detected between SLE and the likelihood of developing bladder cancer or prostate cancer.

Sep 21, 2026

Uploaded by Finn