Exploring the Potential Link Between Autoimmune Diseases and Pan-Cancer - A Multidatabase Mendelian Randomization Analysis

Sep 23, 2026

Uploaded by Kyle

Relationship between autoimmune diseases (AIDs) and cancer remains unclear, especially regarding genetic-level causality. This research used two-sample Mendelian randomization combined with meta-analysis to evaluate associations between genetically predicted AIDs and 33 cancer types, following STROBE-MR guidance. Instrumental variables were AID-associated SNPs from FinnGen, UK Biobank, and other databases, with multiple MR approaches and sensitivity, heterogeneity, and reverse-causality checks. Eight significant results were observed across discovery and replication, providing evidence to support health management guidance for patients with AIDs.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

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Introduction

Methods and Materials

Study Design

Wiley Journal of Immunology Research Volume 2025, Article ID 6468979, 10 pages [https://doi.org/10.1155/jimr/6468979](https://doi.org/10.1155/jimr/6468979) Research Article Exploring the Potential Link Between Autoimmune Diseases and Pan-Cancer: A Multidatabase Mendelian Randomization Analysis Chenguang Wang, Zhiyong Liu, Yuhao Zhou, Yan He, Yashu Zhang, Shiqi Chen, Wenqing Yang, and Lijun Fan Centre for Endemic Disease Control, Chinese Centre for Disease Control and Prevention, Harbin Medical University, Harbin City 150081, Heilongjiang Province, China Correspondence should be addressed to Lijun Fan; [fanlijun@hrbmu.edu.cn](fanlijun@hrbmu.edu.cn) Received 7 December 2024; Accepted 29 March 2025 Academic Editor: Jinyi Tang Copyright © 2025 Chenguang Wang et al. Journal of Immunology Research published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Background: The relationship between autoimmune diseases (AIDs) and cancer is unclear and this study aimed to investigate the relationship between AIDs and cancer at the genetic level using Mendelian randomization (MR) . Methods: The study employed two-sample MR and meta-analysis to investigate the association between AIDs and 33 types of cancer, following STROBE-MR guidelines. Single nucleotide polymorphisms (SNPs) associated with AIDs were used as instrumental variables, with data from FinnGen, UK Biobank, and other databases. MR analyses included sensitivity checks, heterogeneity assessments, and reverse causality tests, using multiple MR methods (inverse-variance weighted (IVW), weighted median, MR-Egger, etc.) . Meta-analysis was performed on validated results to conﬁrm ﬁndings, with statistical analyses conducted using R software. Results: The results identiﬁed eight signiﬁcant associations in both discovery and replication stages. Key ﬁndings include that myasthenia gravis (MG) signiﬁcantly increases the risk of oral cavity cancer, multiple sclerosis (MS) is linked to increased risks of chronic lymphocytic leukemia (CLL) and small intestine cancer, and ulcerative colitis (UC) has mixed effects, reducing the risk of uterine cervix and larynx cancers, but increasing risks for pancreatic and bladder cancers. Meta-analysis conﬁrmed eight secondary ﬁndings, highlighting pathogenic associations such as type 1 diabetes with esophagus cancer and protective effects like systemic lupus erythematosus (SLE) against acute myelocytic leukemia. Conclusions: This study provides evidence of a causal relationship between multiple AIDs and different cancer risks at the genetic level and provides a reference for the health management of patients with AIDs. Keywords: AID; autoimmune disease; cancer; malignancy; UK Biobank 1. Introduction Cancer is a disease characterized by the uncontrolled growth and division of cells. The development of cancer involves genetic mutations, abnormalities in gene expression regulation, and environmental factors, though the precise causes and mechanisms are not yet fully understood. Autoimmune diseases (AIDs) represent a class of disorders where the immune system fails to maintain tolerance to self-antigens, leading to attacks on the body’s own tissues and cells, resulting in chronic inﬂammation and organ damage [1, 2] . Common AIDs include systemic lupus erythematosus(SLE), multiple sclerosis (MS), Crohn’s disease (CD), ulcerative colitis (UC), myasthenia gravis (MG), rheumatoid arthritis (RA), and type 1 diabetes. The chronic inﬂammatory environment associated with AIDs may be linked to cancer development. Additionally, dysregulation of the immune system impairs immune surveillance, allowing abnormal cells to evade timely detection and 2 Journal of Immunology Research elimination. Furthermore, certain treatments for AIDs, such as immunosuppressant

FAQs

What research question does the study address about autoimmune diseases and cancer?

The study investigates whether there is a causal genetic-level relationship between autoimmune diseases (AIDs) and pan-cancer risk.

Which methods and data sources were used in the analysis?

The study applied two-sample Mendelian randomization and meta-analysis, using AID-associated SNPs as instrumental variables from FinnGen, UK Biobank, and other databases, with analyses aligned to STROBE-MR guidelines.

What major findings were reported from discovery and replication stages?

Eight significant associations were identified in both stages, including increased risk links such as myasthenia gravis with oral cavity cancer and multiple sclerosis with chronic lymphocytic leukemia and small intestine cancer.

Sep 23, 2026

Uploaded by Kyle