基因预测的实体癌与败血症风险之间的因果关系：孟德尔随机化研究的见解

Causality of genetically predicted solid cancers on risk of sepsis: insights from Mendelian randomization.

作者信息

Qiu Linjie, Chen Shiyu, Zhong Jia, Zhang Yan, Zhang Kai

机构信息

Department of Anesthesiology and Intensive Care, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

The Children's Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, China.

出版信息

Discov Oncol. 2025 Jun 9;16(1):1043. doi: 10.1007/s12672-025-02848-x.

DOI:10.1007/s12672-025-02848-x

PMID:40490626

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12149036/

Abstract

OBJECTIVE

Some studies have found that solid cancer and sepsis are linked. The primary objective of this study is to explore this connection further, investigating the causal effect of solid cancer on sepsis by applying Mendelian randomization (MR).

METHODS

Using genome-wide association study (GWAS) data from the Medical Research Council-Integrative Epidemiology Unit database, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis to test the causal association between solid cancers (10 GWAS, 1,345,730 samples) and sepsis (2 GWAS, 1,288,566 samples) in European ancestry. In the context of multivariable MR analysis, lifestyle risk factors such as body mass index (BMI) were incorporated, with relevant clinical interventions taken into account.

RESULTS

The two-sample MR analysis suggested a causal relationship between renal cancer and sepsis (OR = 1.051, 95% CI = 1.019-1.085, P = 1.800E-03). Renal cancer (OR = 1.064, 95% CI = 1.011-1.120, P = 1.60E-02), BMI (OR = 1.315, 95% CI = 1.176-1.471, P = 1.25E-06), and smoking (OR = 1.139, 95% CI = 1.009-1.286, P = 3.65E-02) showed a significant association with sepsis in our lifestyle multivariable MR analysis. Reverse MR analysis indicates that sepsis may prevent renal cancer. (OR = 0.924, 95% CI = 0.865 -0.988, P = 2.060E-02).

CONCLUSIONS

Our findings suggest renal cancer is correlated with the occurrence of sepsis. This association is partially influenced by BMI and smoking. Unexpectedly, sepsis may act as a protective effect against renal cancer.

摘要

目的

一些研究发现实体癌与败血症有关联。本研究的主要目的是进一步探究这种联系，通过应用孟德尔随机化（MR）来研究实体癌对败血症的因果效应。

方法

利用医学研究理事会综合流行病学单位数据库中的全基因组关联研究（GWAS）数据，我们进行了双向双样本孟德尔随机化（MR）分析，以检验欧洲血统人群中实体癌（10项GWAS，1345730个样本）与败血症（2项GWAS，1288566个样本）之间的因果关联。在多变量MR分析的背景下，纳入了体重指数（BMI）等生活方式风险因素，并考虑了相关的临床干预措施。

结果

双样本MR分析表明肾癌与败血症之间存在因果关系（比值比[OR]=1.051，95%置信区间[CI]=1.019-1.085，P=1.800×10⁻³）。在我们的生活方式多变量MR分析中，肾癌（OR=1.064，95%CI=1.011-1.120，P=1.60×10⁻²）、BMI（OR=1.315，95%CI=1.176-1.471，P=1.25×10⁻⁶）和吸烟（OR=1.139，95%CI=1.009-1.286，P=3.65×10⁻²）与败血症显示出显著关联。反向MR分析表明败血症可能预防肾癌（OR=0.924，95%CI=0.865-0.988，P=2.060×10⁻²）。