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

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

Linjie Qiu #  1 , Shiyu Chen #  1 , Jia Zhong  1 , Yan Zhang  2 , Kai Zhang  3
Affiliations

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

Linjie Qiu et al. Discov Oncol. .

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, PIVW = 1.800E-03). Renal cancer (OR = 1.064, 95% CI = 1.011-1.120, PIVW = 1.60E-02), BMI (OR = 1.315, 95% CI = 1.176-1.471, PIVW = 1.25E-06), and smoking (OR = 1.139, 95% CI = 1.009-1.286, PIVW = 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, PIVW = 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.

Keywords: Cancer; Causal effect; Genetics; Mendelian randomization analysis; Sepsis risk.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Our analysis used publicly available genome-wide association study (GWAS) summary statistics. No new data were collected, and no new ethical approval was required. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Design of this Mendelian randomization study. SNP, Single nucleotide polymorphisms; GWAS, Genome-wide association study; LD, Linkage disequilibrium
Fig. 2
Fig. 2
Overview of Genome-wide association studies used. ER+, estrogen receptor positive; ER-, estrogen receptor negative; BMI, body mass index; UKb, UK biobank
Fig. 3
Fig. 3
Scatter plot and Funnel plot of MR analysis for significant causal association between Renal cancer and sepsis. A Renal cancer -sepsis(UKb), B Renal cancer -sepsis(UKb), C Renal cancer -sepsis (Finngen), D Renal cancer -sepsis (Finngen). MR: Mendelian Randomization; SNP: Single nucleotide polymorphism;
Fig. 4
Fig. 4
Two-sample MR result (IVW method). ER +, estrogen receptor positive; ER-, estrogen receptor negative
Fig. 5
Fig. 5
Reverse MR result (IVW method). ER +, estrogen receptor positive; ER-, estrogen receptor negative
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References

    1. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229–63. - PubMed
    1. Williams JC, Ford ML, Coopersmith CM. Cancer and sepsis. Clin Sci (Lond). 2023;137(11):881–93. - PMC - PubMed
    1. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016;315(8):801. - PMC - PubMed
    1. Mirouse A, Vigneron C, Llitjos JF, Chiche JD, Mira JP, Mokart D. Sepsis and cancer: an interplay of friends and foes. Am J Respir Crit Care Med. 2020;202(12):1625–35. - PubMed
    1. Danai PA, Moss M, Mannino DM, Martin GS. The epidemiology of sepsis in patients with malignancy. Chest. 2006;129(6):1432–40. - PubMed

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