{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T20:51:23Z","timestamp":1793047883061,"version":"4.5.0"},"reference-count":42,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,7,10]],"date-time":"2020-07-10T00:00:00Z","timestamp":1594339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The human leukocyte antigen (<jats:italic>HLA<\/jats:italic>) locus on chromosome 6 has been reported to be associated with cervical cancer. We investigated two independent single\u2010nucleotide polymorphisms in a large case\u2010control series of cervical dysplasia and carcinoma that has been newly established by the German Cervigen Consortium, comprising a total of 2481 cases and 1556 healthy females. We find significant associations for both variants, rs9272117 at <jats:italic>HLA\u2010DQA1<\/jats:italic> and rs2844511 at <jats:italic>MICA<\/jats:italic> and <jats:italic>HCP5<\/jats:italic>, with cervical disease. Both variants showed evidence of association with invasive cervical cancer (rs9272117: OR 0.89, 95% CI 0.79\u20100.99, <jats:italic>P<\/jats:italic> = .036; rs2844511: OR 1.17, 95% CI 1.04\u20101.31, <jats:italic>P<\/jats:italic> = .008) and with high\u2010grade dysplasia (rs9272117: OR 0.78, 95% CI 0.70\u20100.87, <jats:italic>P<\/jats:italic> = 7.1 \u00d7\u200910<jats:sup>\u22126<\/jats:sup>; rs2844511: OR 1.13, 95% CI 1.01\u20101.26, <jats:italic>P<\/jats:italic> = .035), as well as in a combined analysis of both groups (rs9272117: OR 0.83, 95% CI 0.75\u20100.91, <jats:italic>P<\/jats:italic> = 6.9 \u00d7\u200910<jats:sup>\u22125<\/jats:sup>; rs2844511: OR 1.14, 95% CI 1.04\u20101.26, <jats:italic>P<\/jats:italic> = .005). Variant rs2844511, but not rs9272117, also showed modest evidence of association with low\u2010grade dysplasia (OR 1.26, 95% CI 1.04\u20101.54, <jats:italic>P<\/jats:italic> = .019). In case\u2010only analyses, rs2844511 tended to predict HPV status (<jats:italic>P<\/jats:italic> = .044) and rs9272117 tended to associate with HPV16 (<jats:italic>P<\/jats:italic> = .022). RNA studies in cervical samples showed a significant correlation in the transcript levels of <jats:italic>MICA<\/jats:italic>, <jats:italic>HCP5<\/jats:italic> and <jats:italic>HLA\u2010DQA1<\/jats:italic>, suggesting extensive co\u2010regulation. All three genes were upregulated in HPV16\u2010positive samples. In stratified analyses, rs9272117 was associated with <jats:italic>HLA\u2010DQA1<\/jats:italic> levels, specifically in HPV\u2010positive samples, while rs2844511 was associated with <jats:italic>MICA<\/jats:italic> and <jats:italic>HCP5<\/jats:italic> levels. The risk allele of rs2844511 was required for correlations between <jats:italic>MICA<\/jats:italic> or <jats:italic>HCP5<\/jats:italic> with <jats:italic>HLA\u2010DQA1<\/jats:italic>. Altogether, our results support 6p21.32\u201033 as the first consistent cervical cancer susceptibility locus and provide evidence for a link between genetic risk variants, HPV16 status and transcript levels of <jats:italic>HLA\u2010DQA1<\/jats:italic>, <jats:italic>HCP5<\/jats:italic> and <jats:italic>MICA<\/jats:italic>, which may contribute to tumor immune evasion.<\/jats:p>","DOI":"10.1002\/ijc.33171","type":"journal-article","created":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T21:06:46Z","timestamp":1593032806000},"page":"2458-2468","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Association of genomic variants at the human leukocyte antigen locus with cervical cancer risk, <scp>HPV<\/scp> status and gene expression levels"],"prefix":"10.1002","volume":"147","author":[{"given":"Dhanya","family":"Ramachandran","sequence":"first","affiliation":[{"name":"Department of Gynaecology, Comprehensive Cancer Center Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Sch\u00fcrmann","sequence":"additional","affiliation":[{"name":"Department of Gynaecology, Comprehensive Cancer Center Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Gynaecology, Comprehensive Cancer Center Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gynaecology, Comprehensive Cancer Center Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa\u2010Marie","family":"Bretschneider","sequence":"additional","affiliation":[{"name":"Department of Gynaecology, Comprehensive Cancer Center Hannover Medical School  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