{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T07:54:28Z","timestamp":1780559668494,"version":"3.54.1"},"reference-count":45,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2024,8,3]],"date-time":"2024-08-03T00:00:00Z","timestamp":1722643200000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hypoxia is often involved in tumor microenvironment, and the hypoxia\u2010induced signaling pathways play a key role in aggressive cancer phenotypes, including angiogenesis, immune evasion, and therapy resistance. However, it is unknown what role genetic variants in the hypoxia\u2010related genes play in survival of patients with non\u2010small cell lung cancer (NSCLC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We evaluated the associations between 16,092 single\u2010nucleotide polymorphisms (SNPs) in 182 hypoxia\u2010related genes and survival outcomes of NSCLC patients. Data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial were used as the discovery dataset, and the Harvard Lung Cancer Susceptibility (HLCS) Study served as the replication dataset. We also performed additional linkage disequilibrium analysis and a stepwise multivariable Cox proportional hazards regression analysis in the PLCO dataset.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>An independent SNP, <jats:italic>ERRFI1<\/jats:italic> rs28624 A\u2009&gt;\u2009C, was identified with an adjusted hazards ratio (HR) of 1.31 (95% CI\u2009=\u20091.14\u20131.51, <jats:italic>p<\/jats:italic>\u2009=\u20090.0001) for overall survival (OS). In further analyses, unfavorable genotypes AC and CC, compared with the AA genotype, were associated a worse OS (HR\u2009=\u20091.20, 95% CI\u2009=\u20091.03\u20131.39, <jats:italic>p<\/jats:italic>\u2009=\u20090.014) and disease\u2010specific survival (HR\u2009=\u20091.21, 95% CI\u2009=\u20091.04\u20131.42, <jats:italic>p<\/jats:italic>\u2009=\u20090.016). Further expression quantitative trait loci analysis indicated that <jats:italic>ERRFI1<\/jats:italic> rs28624C genotypes were significantly associated with higher <jats:italic>ERRFI1<\/jats:italic> mRNA expression levels in the whole blood. Additional analysis showed that high <jats:italic>ERRFI1<\/jats:italic> mRNA expression levels were associated with a worse OS in patients with lung adenocarcinoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings suggest that genetic variants in the hypoxia\u2010related gene <jats:italic>ERRFI1<\/jats:italic> may modulate NSCLC survival, potentially through their effect on the gene expression.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.70073","type":"journal-article","created":{"date-parts":[[2024,8,3]],"date-time":"2024-08-03T08:43:36Z","timestamp":1722674616000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Potentially functional variants of <i>ERRFI1<\/i> in hypoxia\u2010related genes predict survival of non\u2010small cell lung cancer patients"],"prefix":"10.1002","volume":"13","author":[{"given":"Huilin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Respiratory Oncology, Guangxi Cancer Hospital Guangxi Medical University Cancer Hospital  Nanning Guangxi China"},{"name":"Duke Cancer Institute, Duke University Medical Center  Durham North Carolina USA"},{"name":"Department of Population Health Sciences Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongliang","family":"Liu","sequence":"additional","affiliation":[{"name":"Duke Cancer Institute, Duke University Medical Center  Durham North Carolina USA"},{"name":"Department of Population Health Sciences Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guojun","family":"Lu","sequence":"additional","affiliation":[{"name":"Duke Cancer Institute, Duke University Medical Center  Durham North 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mulong","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Environmental Health and Department of Epidemiology Harvard TH Chan School of Public Health  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Christiani","sequence":"additional","affiliation":[{"name":"Department of Environmental Health and Department of Epidemiology Harvard TH Chan School of Public Health  Boston Massachusetts USA"},{"name":"Department of Medicine Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3845-9445","authenticated-orcid":false,"given":"Qingyi","family":"Wei","sequence":"additional","affiliation":[{"name":"Duke Cancer Institute, Duke University Medical Center  Durham North Carolina USA"},{"name":"Department of Population Health Sciences Duke 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