Causal relationship between infection and gastrointestinal cancers: a multivariable Mendelian randomization study.

IF 2.1 4区医学 Q3 ONCOLOGY

Chinese clinical oncology Pub Date : 2025-06-01 DOI:10.21037/cco-24-126

Ruopeng Zhang, Yinghe Li, Yuqian Huang, Lei Liu, Shatong Li, Bowen Huang, Wanqi Chen

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引用次数: 0

Abstract

Background: The association between infection and gastrointestinal cancers (GICs) were indicated by pervious studies, but the direct causal link between infection and GIC remains largely unknown. We performed multivariable mendelian randomization (MR) analyses in order to investigate the causal relationship between genetically predicted infection and the GIC risk.

Methods: Instrumental variables (IVs) for several common pathogens including Helicobacter pylori (H. pylori), human papillomavirus (HPV) and herpesvirus were retrieved from different genome-wide association studies (GWAS), respectively. The summary-level statistics of GIC were obtained from the European heritage. The inverse-variance weighted MR was conducted as the main approach followed by multiple sensitivity analyses. Twenty datasets of seropositivity and antigen antibody levels against infectious pathogens were utilized as IVs. Four GWAS datasets of GIC were retrieved.

Results: It is notable that no evidence demonstrated the causal relationship of H. pylori with gastric cancer (GC) in European ancestry. Several infectious agents were proposed as protective factors for GIC in European population. MR results showed that anti-Epstein-Barr virus (EBV) immunoglobulin G (IgG) seropositivity [odds ratio (OR) =0.32, 95% confidence interval (CI): 0.11-0.95] and EBV ZEBRA antibody levels (OR =0.74, 95% CI: 0.58-0.94) was negatively correlated with the risk of GC. Genetical predisposition of herpes simplex virus (HSV) infection showed a negative correlation with the risk of colon cancer. Similarly, increased levels of H. pylori GroEL antibody also exhibited as a protective factor for colorectal cancer (CRC; OR =0.80, 95% CI: 0.69-0.93).

Conclusions: The results reflected differential patterns of geographically distribution and pathogenic role of infectious pathogens among diverse population. Human and infection pathogens co-evolution shape the risk of cancers.

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感染与胃肠道癌症的因果关系：一项多变量孟德尔随机研究。

背景：先前的研究表明感染与胃肠道癌症（GIC）之间存在关联，但感染与GIC之间的直接因果关系在很大程度上仍然未知。为了研究遗传预测感染与GIC风险之间的因果关系，我们进行了多变量孟德尔随机化（MR）分析。方法：分别从不同的全基因组关联研究（GWAS）中检索幽门螺杆菌（Helicobacter pylori）、人乳头瘤病毒（human papillomavirus， HPV）和疱疹病毒（herpesvirus）等几种常见病原体的工具变量。GIC的汇总统计数据来自欧洲遗产。以反方差加权MR为主要方法，其次进行多重敏感性分析。使用20个血清阳性和抗原抗体水平数据集作为iv。检索4个GIC的GWAS数据集。结果：值得注意的是，没有证据表明幽门螺杆菌与胃癌（GC）在欧洲血统的因果关系。几种传染因子被认为是欧洲人群中GIC的保护因素。MR结果显示，抗eb病毒（EBV）免疫球蛋白G （IgG）血清阳性[比值比(OR) =0.32, 95%可信区间（CI）： 0.11-0.95]和EBV ZEBRA抗体水平（OR =0.74, 95% CI: 0.58-0.94）与胃癌发生风险呈负相关。单纯疱疹病毒（HSV）感染的遗传易感性与结肠癌的风险呈负相关。同样，幽门螺杆菌GroEL抗体水平的升高也被证明是结直肠癌(CRC；Or =0.80, 95% ci: 0.69-0.93)。结论：研究结果反映了传染性病原体在不同人群中的地理分布和致病作用的差异。人类和感染病原体共同进化形成癌症的风险。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Chinese clinical oncology ONCOLOGY-

CiteScore

3.90

自引率

0.00%

发文量

期刊介绍： The Chinese Clinical Oncology (Print ISSN 2304-3865; Online ISSN 2304-3873; Chin Clin Oncol; CCO) publishes articles that describe new findings in the field of oncology, and provides current and practical information on diagnosis, prevention and clinical investigations of cancer. Specific areas of interest include, but are not limited to: multimodality therapy, biomarkers, imaging, tumor biology, pathology, chemoprevention, and technical advances related to cancer. The aim of the Journal is to provide a forum for the dissemination of original research articles as well as review articles in all areas related to cancer. It is an international, peer-reviewed journal with a focus on cutting-edge findings in this rapidly changing field. To that end, Chin Clin Oncol is dedicated to translating the latest research developments into best multimodality practice. The journal features a distinguished editorial board, which brings together a team of highly experienced specialists in cancer treatment and research. The diverse experience of the board members allows our editorial panel to lend their expertise to a broad spectrum of cancer subjects.