{"title":"Mendelian randomization analysis for identifying circulating inflammatory cytokines and risk of pancreatic cancers.","authors":"Yangni Li, Ruoshu Duan, Mengjie Hu, Ying Liu, Xiaochen Zhang, Jingjing Ren","doi":"10.1093/postmj/qgaf056","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>Inflammation is intricately linked to the emergence and advancement of most cancers, playing a pivotal role in their malignant transformation. Observational evidence revealed the role of cytokines in pancreatic cancer (PC) carcinogenesis. However, observational studies may be limited by small sample sizes, confounding factors, and reverse causality when establishing a correlation between inflammatory cytokines and PC risk.</p><p><strong>Design: </strong>Conducting a two-sample Mendelian randomization analysis, we investigated the potential relationship between inflammatory cytokines in circulation and pancreatic cancer. Data from the most extensive genome-wide association studies (GWAS) on cytokines were utilized, involving 31 112 individuals of European descent. Additionally, the PC GWAS from the Integrative Epidemiology Unit (IEU) analysis of Finnish Biobank data was included, consisting of 605 PC cases and 218 187 controls of European ancestry.</p><p><strong>Results: </strong>Around 47 cytokines were systematically screened, which revealed that circulating levels of IL-1ra (OR: 0.63; 95% CIs: 0.46-0.87; P-value: 4.9 × 10-4), IP-10 (OR: 0.33; 95% CIs: 0.18-0.59; P-value: 1.8 × 10-4) and macrophage inflammatory protein (MIP)-1a (OR: 1.37; 95% CIs: 1.08-1.75; P-value: 1 × 10-2) predicted by genetic criteria were prominently linked to an elevated risk of overall PC.</p><p><strong>Conclusion: </strong>Further evidence indicates that certain inflammatory cytokines play critical roles in PC carcinogenesis and that specific inflammatory cytokines can be targeted to prevent PC. Nevertheless, additional research is necessary to assess the potential of these cytokines in detecting PC at an early stage.</p>","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":""},"PeriodicalIF":3.6000,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Postgraduate Medical Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/postmj/qgaf056","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0
Abstract
Objectives: Inflammation is intricately linked to the emergence and advancement of most cancers, playing a pivotal role in their malignant transformation. Observational evidence revealed the role of cytokines in pancreatic cancer (PC) carcinogenesis. However, observational studies may be limited by small sample sizes, confounding factors, and reverse causality when establishing a correlation between inflammatory cytokines and PC risk.
Design: Conducting a two-sample Mendelian randomization analysis, we investigated the potential relationship between inflammatory cytokines in circulation and pancreatic cancer. Data from the most extensive genome-wide association studies (GWAS) on cytokines were utilized, involving 31 112 individuals of European descent. Additionally, the PC GWAS from the Integrative Epidemiology Unit (IEU) analysis of Finnish Biobank data was included, consisting of 605 PC cases and 218 187 controls of European ancestry.
Results: Around 47 cytokines were systematically screened, which revealed that circulating levels of IL-1ra (OR: 0.63; 95% CIs: 0.46-0.87; P-value: 4.9 × 10-4), IP-10 (OR: 0.33; 95% CIs: 0.18-0.59; P-value: 1.8 × 10-4) and macrophage inflammatory protein (MIP)-1a (OR: 1.37; 95% CIs: 1.08-1.75; P-value: 1 × 10-2) predicted by genetic criteria were prominently linked to an elevated risk of overall PC.
Conclusion: Further evidence indicates that certain inflammatory cytokines play critical roles in PC carcinogenesis and that specific inflammatory cytokines can be targeted to prevent PC. Nevertheless, additional research is necessary to assess the potential of these cytokines in detecting PC at an early stage.
期刊介绍：
Postgraduate Medical Journal is a peer reviewed journal published on behalf of the Fellowship of Postgraduate Medicine. The journal aims to support junior doctors and their teachers and contribute to the continuing professional development of all doctors by publishing papers on a wide range of topics relevant to the practicing clinician and teacher. Papers published in PMJ include those that focus on core competencies; that describe current practice and new developments in all branches of medicine; that describe relevance and impact of translational research on clinical practice; that provide background relevant to examinations; and papers on medical education and medical education research. PMJ supports CPD by providing the opportunity for doctors to publish many types of articles including original clinical research; reviews; quality improvement reports; editorials, and correspondence on clinical matters.
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