感染与胃肠道癌症之间的因果关系：一项多变量孟德尔随机化研究

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

作者信息

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

机构信息

Department of Gastric Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China.

Department of Nuclear Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China.

出版信息

Chin Clin Oncol. 2025 Jun;14(3):31. doi: 10.21037/cco-24-126.

DOI:10.21037/cco-24-126

PMID:40575968

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.

摘要

背景

以往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仍 largely未知。我们进行了多变量孟德尔随机化（MR）分析，以研究基因预测的感染与GIC风险之间的因果关系。

方法

分别从不同的全基因组关联研究（GWAS）中检索包括幽门螺杆菌（H. pylori）、人乳头瘤病毒（HPV）和疱疹病毒在内的几种常见病原体的工具变量（IVs）。GIC的汇总统计数据来自欧洲血统人群。以逆方差加权MR作为主要方法，并进行多次敏感性分析。使用了20个针对感染性病原体的血清阳性和抗原抗体水平数据集作为IVs。检索了4个GIC的GWAS数据集。

结果

值得注意的是，在欧洲血统人群中，没有证据表明幽门螺杆菌与胃癌（GC）存在因果关系。在欧洲人群中，几种感染因子被认为是GIC的保护因素。MR结果显示，抗爱泼斯坦-巴尔病毒（EBV）免疫球蛋白G（IgG）血清阳性[比值比（OR）=0.32，95%置信区间（CI）：0.11-0.95]和EBV ZEBRA抗体水平（OR =0.74，95%CI：0.58-0.94）与GC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风险呈负相关。同样，幽门螺杆菌GroEL抗体水平升高也表现为结直肠癌（CRC）的保护因素（OR =0.80，95%CI：0.69-0.93）。