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孟德尔随机化分析揭示了炎症性肠病与子宫颈肿瘤之间因果关系的遗传证据。

Mendelian randomization analysis reveals genetic evidence for a causal link between inflammatory bowel disease and uterine cervical neoplasms.

作者信息

Cao Chunge, Sun Xiaorui, Chen Xiaohu, Zhang Ying, Yue Chaoyan

机构信息

Department of Obstetrics and Gynecology, Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Shanghai YK Pao School, Shanghai, China.

出版信息

Front Genet. 2025 Jan 28;15:1436512. doi: 10.3389/fgene.2024.1436512. eCollection 2024.

Abstract

BACKGROUND

Inflammatory bowel disease (IBD) has been reported to be associated with risk of uterine cervical neoplasm. We aimed to evaluate the causal relationship between IBD and uterine cervical neoplasm using a bidirectional Mendelian randomization analysis.

METHODS

We derived instrumental variables for IBD, including Crohn's disease and ulcerative colitis, from the IEU Open genome-wide association study (GWAS) database, and for the histological subtypes of uterine cervical neoplasm from the FinnGen repository's GWAS data. The collected GWAS data predominantly represent individuals of European ancestry. The inverse-variance weighted (IVW) method was employed as primary analysis approach.

RESULTS

IBD (IVW odds ratio = 1.127, 95% confidence interval = 1.016-1.251; = 0.024) and CD (IVW odds ratio = 1.119, 95% confidence interval = 1.023-1.224; = 0.014) exhibited a significant causal effect on malignant cervical carcinoma. Sensitivity analyses confirmed these findings.

CONCLUSION

Genetically predicted IBD and CD are risk factors for the development of malignant cervical carcinoma. Patients with IBD and CD require specific attention to prevent cervical squamous cell carcinoma. Further studies to elucidate the underlying mechanisms may reveal new therapeutic targets.

摘要

背景

据报道,炎症性肠病(IBD)与子宫颈肿瘤风险相关。我们旨在使用双向孟德尔随机化分析评估IBD与子宫颈肿瘤之间的因果关系。

方法

我们从IEU开放全基因组关联研究(GWAS)数据库中获取IBD的工具变量,包括克罗恩病和溃疡性结肠炎,并从芬兰基因库的GWAS数据中获取子宫颈肿瘤组织学亚型的工具变量。收集的GWAS数据主要代表欧洲血统的个体。采用逆方差加权(IVW)方法作为主要分析方法。

结果

IBD(IVW比值比 = 1.127,95%置信区间 = 1.016 - 1.251;P = 0.024)和克罗恩病(IVW比值比 = 1.119,95%置信区间 = 1.023 - 1.224;P = 0.014)对子宫颈恶性肿瘤表现出显著的因果效应。敏感性分析证实了这些发现。

结论

基因预测的IBD和克罗恩病是子宫颈恶性肿瘤发生的危险因素。IBD和克罗恩病患者需要特别关注以预防宫颈鳞状细胞癌。进一步阐明潜在机制的研究可能会揭示新的治疗靶点。

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