{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T21:47:57Z","timestamp":1784238477503,"version":"3.55.0"},"reference-count":52,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Autophagy plays a multifaceted role in tumorigenesis. However, the association between genetic variants in autophagy and gastric cancer susceptibility remains unclear. We evaluated the association between single\u2010nucleotide polymorphisms (SNPs) of autophagy\u2010related genes and gastric cancer risk using a cohort of 1,625 cases and 2,100 controls. Next, transcriptomic data were used to analyze differential gene expression and characterize the tumor immune microenvironment (TME). Single\u2010cell RNA sequencing analysis was performed to investigate cell\u2010type\u2010specific expression profiles. In vitro gain\/loss\u2010of\u2010function experiments were conducted to explore the biological roles of <jats:italic>TRAF6<\/jats:italic> in cancer cells. We found that <jats:italic>TRAF6<\/jats:italic> rs5030437 G\u2009&gt;\u2009A conferred an increased risk of gastric cancer (OR\u2009=\u20091.23, 95% CI: 1.06\u20101.43, <jats:italic>p<\/jats:italic>\u2009=\u20091.28 \u00d7 10<jats:sup>\u22123<\/jats:sup>), particularly in males (OR\u2009=\u20091.24, 95% CI: 1.07\u20131.44, <jats:italic>p<\/jats:italic>\u2009=\u20093.69 \u00d7 10<jats:sup>\u22123<\/jats:sup>) and older individuals (OR\u2009=\u20091.41, 95% CI: 1.18\u20131.68, <jats:italic>p<\/jats:italic>\u2009=\u20091.53 \u00d7 10<jats:sup>\u22124<\/jats:sup>). <jats:italic>TRAF6<\/jats:italic> expression was significantly upregulated in tumor tissues, correlating with poor prognosis in gastric cancer patients. Enrichment analyses implicated <jats:italic>TRAF6<\/jats:italic> in immune response and inflammation signaling, manifested as its characteristic cellular expression distribution and influence on the abundance of specific immune cells. In vitro experiments demonstrated that <jats:italic>TRAF6<\/jats:italic> positively regulated autophagy activity and promoted cell viability, migration, and proliferation of gastric cancer cells, which were reversed by autophagy inhibition. This study elucidated the genetic association of rs5030437 G\u2009&gt;\u2009A and gastric cancer as well as the impacts of <jats:italic>TRAF6<\/jats:italic> on TME dynamics and cancer biology, which provided novel insights into gastric carcinogenesis and the tumor ecosystem.<\/jats:p>","DOI":"10.1002\/mc.70032","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T06:45:46Z","timestamp":1755672346000},"page":"1860-1871","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<i>TRAF6<\/i> Exerts Tumor\u2010Promoting Effects via Genetic and Autophagic Modulation in Gastric Cancer"],"prefix":"10.1002","volume":"64","author":[{"given":"Yifan","family":"Zou","sequence":"first","affiliation":[{"name":"Department of General Surgery The First Affiliated Hospital of Nanjing Medical University Nanjing China"},{"name":"Departments of Environmental Genomics and Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health Nanjing Medical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenguang","family":"Mao","sequence":"additional","affiliation":[{"name":"Departments of Environmental Genomics and Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health Nanjing Medical University Nanjing China"},{"name":"Department of Physical and Chemical Testing, School of Medical Technology Jiangsu College of Nursing Huai\u2032an 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