{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T21:21:47Z","timestamp":1792531307276,"version":"4.5.0"},"reference-count":73,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T00:00:00Z","timestamp":1622419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["OPUS 8 2014\/15\/B\/NZ5\/03517"],"award-info":[{"award-number":["OPUS 8 2014\/15\/B\/NZ5\/03517"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Lung cancer is strongly associated with cigarette smoking; nevertheless some never-smokers develop cancer. Immune eradication of cancer cells is dependent on polymorphisms of HLA class I molecules and antigen-processing machinery (APM) components. We have already published highly significant associations of single nucleotide polymorphisms (SNPs) of the <jats:italic>ERAP1<\/jats:italic> gene with non-small cell lung cancer (NSCLC) in Chinese, but not in Polish populations. However, the smoking status of participants was not known in the previous study. Here, we compared the distribution of APM polymorphic variants in larger cohorts of Polish patients with NSCLC and controls, stratified according to their smoking status. We found significant but opposite associations in never-smokers and in smokers of all tested SNPs (<jats:italic>rs26653, rs2287987, rs30187<\/jats:italic>, and <jats:italic>rs27044<\/jats:italic>) but one (<jats:italic>rs26618<\/jats:italic>) in <jats:italic>ERAP1<\/jats:italic>. No significant associations were seen in other genes. Haplotype analysis indicated that the distribution of many <jats:italic>ERAP1\/2<\/jats:italic> haplotypes is opposite, depending on smoking status. Additionally, haplotypic combination of low activity ERAP1 and the lack of an active form of ERAP2 seems to favor the disease in never-smokers. We also revealed interesting associations of some APM polymorphisms with: age at diagnosis (<jats:italic>ERAP1 rs26653<\/jats:italic>), disease stage (<jats:italic>ERAP1 rs27044<\/jats:italic>, <jats:italic>PSMB9 rs17587<\/jats:italic>), overall survival (<jats:italic>ERAP1 rs30187<\/jats:italic>), and response to chemotherapy (<jats:italic>ERAP1 rs27044<\/jats:italic>). The results presented here may suggest the important role for ERAP1 in the anti-cancer response, which is different in smokers <jats:italic>versus<\/jats:italic> never-smokers, depending to some extent on the presence of ERAP2, and affecting NSCLC clinical course.<\/jats:p>","DOI":"10.3389\/fimmu.2021.664474","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T07:53:47Z","timestamp":1622447627000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Polymorphisms of Antigen-Presenting Machinery Genes in Non-Small Cell Lung Cancer: Different Impact on Disease Risk and Clinical Parameters in Smokers and Never-Smokers"],"prefix":"10.3389","volume":"12","author":[{"given":"Andrzej","family":"Wi\u015bniewski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Sobczy\u0144ski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konrad","family":"Pawe\u0142czyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irena","family":"Por\u0119bska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Jasek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanda","family":"Niepiek\u0142o-Miniewska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneta","family":"Kowal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Dubis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"J\u0119druchniewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Ku\u015bnierczyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.07-0442","article-title":"Differences in Epidemiology, Histology, and Survival Between Cigarette Smokers and Never-Smokers Who Develop Non-Small Cell Lung Cancer","volume":"132","author":"Bryant","year":"2007","journal-title":"Chest"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.rcl.2012.06.006","article-title":"Lung Cancer Epidemiology, Risk Factors, and Prevention","volume":"50","author":"de Groot","year":"2012","journal-title":"Radiol Clin North Am"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.soc.2016.02.001","article-title":"Epidemiology of Lung Cancer","volume":"25","author":"Mao","year":"2016","journal-title":"Surg Oncol Clin N Am"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.4065\/83.5.584","article-title":"Non-Small Cell Lung Cancer: Epidemiology, Risk Factors, Treatment, and Survivorship","volume":"83","author":"Molina","year":"2008","journal-title":"Mayo Clin Proc"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2018.12.006","article-title":"Lung Cancer","volume":"103","author":"Nasim","year":"2019","journal-title":"Med Clin North Am"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.3390\/cancers12051196","article-title":"Oncogene-Addicted Non-Small-Cell Lung Cancer: Treatment Opportunities and Future Perspectives","volume":"12","author":"Ferrara","year":"2020","journal-title":"Cancers (Basel)"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0169-5002(95)00566-8","article-title":"Aspects of the Epidemiology of Lung Cancer in Smokers and Nonsmokers in the United States","volume":"15","author":"Kabat","year":"1996","journal-title":"Lung Cancer"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2190","article-title":"Lung Cancer in Never Smokers\u2013a Different Disease","volume":"7","author":"Sun","year":"2007","journal-title":"Nat Rev Cancer"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.currproblcancer.2017.07.002","article-title":"Risk Factors of Lung Cancer in Nonsmoker","volume":"41","author":"Akhtar","year":"2017","journal-title":"Curr Probl Cancer"},{"key":"B10","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1007\/978-3-319-24223-1_3","article-title":"Lung Cancer in Never Smokers","volume":"893","author":"Rivera","year":"2016","journal-title":"Adv Exp Med Biol"},{"key":"B11","article-title":"HLA and Infectious Diseases. 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