中国癌症防治杂志2026，Vol.18Issue(4)：434-444,11.DOI:10.27054/j.cnki.ISSN.1674-5671.2026.04.06
基于全基因组关联分析揭示炎症性肠病与口腔/口咽癌间的共享遗传结构
Genome-wide association analysis reveals shared genetic architecture between inflammatory bowel disease and oral and oropharyngeal cancer
摘要
Abstract
Objective To systematically investigate the shared genetic architecture between inflammatory bowel disease(IBD)and oral and oropharyngeal cancer.Methods We integrated genome-wide association study(GWAS)summary data for IBD and oral and oropharyngeal cancer in European populations.Linkage disequilibrium score regression was used to estimate their genetic correlation,and cross-trait meta-analysis was performed to identify shared susceptibility loci.Four gene-based approaches,including transcriptome-wide association studies(TWAS),summary-data-based Mendelian randomization(SMR),multi-marker analysis of genomic annotation(MAGMA),and fast set-based association test(fastBAT),were jointly applied to identify shared genes,followed by pathway and tissue/cell-type enrichment analyses.Single-cell Mendelian randomization was employed to identify cell-type-specific potential causal genes,and pathway matching was used to screen for potential therapeutic agents for the comorbidity.Key findings were validated in independent FinnGen and UK Biobank datasets.Results IBD and oral and oropharyngeal cancer showed a suggestive positive genetic correlation(rg=0.303,P=0.037,PFDR=0.167),with a consistent direction in the validation set(rg=0.281,P=0.031,PFDR=0.267).An independent shared genetic risk locus,rs17612816,was identified on chromosome 6 in the HLA-DQA1/HLA-DQB1 genes.Integrative multi-method analyses identified 1,132 shared genes,of which 31 were high-confidence shared genes.Functional enrichment revealed that these genes were predominantly involved in immune pathways including T-cell differentiation,MHC class Ⅱ mediated antigen processing and presentation,and JAK-STAT signaling.Tissue and cell-type enrichment analyses further showed enrichment in tissues such as the lung,spleen,and peripheral blood,as well as in immune cell types including T cells and macrophages.Single-cell Mendelian ran-domization identified 92 candidate causal genes in specific immune cell subsets,15 of which were supported by colocalization evidence.Small-molecule inhibitors targeting the JAK-STAT pathway showed the strongest match for the comorbidity of IBD and oral and oropharyngeal cancer.Conclusions Our findings suggest a potential genetic overlap between IBD and oral and oropharyngeal cancer in European popu-lations,with the shared signals mapped to the HLA-DQA1/HLA-DQB1 genes on chromosome 6 and highly enriched in immune pathways including T-cell differentiation,MHC class Ⅱ-mediated antigen processing and presentation,and JAK-STAT signaling.关键词
炎症性肠病/口腔癌/口咽癌/遗传相关性/全基因组关联研究/共享遗传结构Key words
Inflammatory bowel disease/Oral cancer/Oropharyngeal cancer/Genetic correlation/Genome-wide association studies/Shared genetic architecture分类
医药卫生引用本文复制引用
吴净涵,白英杰,程傲铭,冯芝恩..基于全基因组关联分析揭示炎症性肠病与口腔/口咽癌间的共享遗传结构[J].中国癌症防治杂志,2026,18(4):434-444,11.基金项目
国家自然科学基金项目(82573934) （82573934）
北京高层次创新创业人才支持计划青年拔尖人才(G202522151) （G202522151）
首都卫生发展科研专项项目(首发2026-2-2142) （首发2026-2-2142）
北京市自然科学基金项目(7252058) （7252058）
