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炎症性肠病与肠外恶性肿瘤风险的关联:两样本孟德尔随机研究。

Association between inflammatory bowel disease and the risk of parenteral malignancies: A two-sample Mendelian randomization study.

机构信息

Department of Digestive Disease, The First People's Hospital of Foshan City, Guangdong, P.R. China.

Department of Digestive Disease, The First People's Hospital of Foshan City, Guangdong, P.R. China.

出版信息

Clinics (Sao Paulo). 2024 Jun 27;79:100421. doi: 10.1016/j.clinsp.2024.100421. eCollection 2024.

Abstract

AIM

Using Mendelian Randomization (MR) analysis to investigate the potential causal association between Inflammatory Bowel Disease (IBD) and the occurrence of parenteral malignancies, in order to provide some reference for the parenteral malignancy prevention in patients with IBD.

METHODS

This was a two-sample MR study based on independent genetic variants strongly linked to IBD selected from the Genome-Wide Association Study (GWAS) meta-analysis carried out by the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). Parenteral malignancy cases and controls were obtained from the FinnGen consortium and the UK Biobank (UKB) release data. Inverse Variance Weighted (IVW), weighted median, MR-Egger, and strength test (F) were utilized to explore the causal association of IBD with parenteral malignancies. In addition, Cochran's Q statistic was performed to quantify the heterogeneity of Instrumental Variables (IVs).

RESULTS

The estimates of IVW showed that patients with IBD had higher odds of diffuse large B-cell lymphoma (OR = 1.2450, 95% CI: 1.0311‒1.5034). UC had potential causal associations with non-melanoma skin cancer (all p < 0.05), melanoma (OR = 1.0280, 95% CI: 0.9860‒1.0718), and skin cancer (OR = 1.0004, 95% CI: 1.0001‒1.0006). Also, having CD was associated with higher odds of non-melanoma skin cancer (all p < 0.05) and skin cancer (OR = 1.0287, 95% CI: 1.0022‒1.0559). In addition, results of pleiotropy and heterogeneity tests indicated these results are relatively robust.

CONCLUSIONS

IBD has potential causal associations with diffuse large B-cell lymphoma and skin cancers, which may provide some information on the prevention of parenteral malignancies in patients with IBD. Moreover, further studies are needed to explore the specific mechanisms of the effect of IBD on skin cancers.

摘要

目的

采用孟德尔随机化(MR)分析探讨炎症性肠病(IBD)与肠外恶性肿瘤发生之间的潜在因果关系,为 IBD 患者的肠外恶性肿瘤预防提供参考。

方法

本研究基于国际炎症性肠病遗传学联盟(IIBDGC)进行的全基因组关联研究(GWAS)荟萃分析中选择的与 IBD 强烈相关的独立遗传变异,采用两样本 MR 研究。肠外恶性肿瘤病例和对照来自芬兰基因研究(FinnGen)联盟和英国生物银行(UKB)发布的数据。采用逆方差加权(IVW)、加权中位数、MR-Egger 和强度检验(F)来探讨 IBD 与肠外恶性肿瘤的因果关系。此外,采用 Cochran's Q 统计量来量化工具变量(IVs)的异质性。

结果

IVW 估计表明,IBD 患者发生弥漫性大 B 细胞淋巴瘤的几率更高(OR = 1.2450,95%CI:1.0311‒1.5034)。UC 与非黑色素瘤皮肤癌(均 P < 0.05)、黑色素瘤(OR = 1.0280,95%CI:0.9860‒1.0718)和皮肤癌(OR = 1.0004,95%CI:1.0001‒1.0006)之间存在潜在因果关系。此外,CD 与非黑色素瘤皮肤癌(均 P < 0.05)和皮肤癌(OR = 1.0287,95%CI:1.0022‒1.0559)发生几率更高相关。此外,多效性和异质性检验结果表明,这些结果相对稳健。

结论

IBD 与弥漫性大 B 细胞淋巴瘤和皮肤癌之间存在潜在因果关系,这可能为 IBD 患者的肠外恶性肿瘤预防提供一定信息。此外,需要进一步研究以探讨 IBD 对皮肤癌影响的具体机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7dd/11260596/bae8b2ec3c39/gr1.jpg

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