A variant upstream of HLA-DRB1 and multiple variants in MICA influence susceptibility to cervical cancer in a Swedish population
In a genome-wide association study, we have previously identified and performed the initial replication of three novel susceptibility loci for cervical cancer: rs9272143 upstream of HLA-DRB1, rs2516448 adjacent to MHC class I polypeptide-related sequence A gene (MICA), and rs3117027 at HLA-DPB2. The...
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Uppsala universitet, Institutionen för immunologi, genetik och patologi
2014
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Online Access: | http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-238030 https://doi.org/10.1002/cam4.183 |
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ftuppsalauniv:oai:DiVA.org:uu-238030 2024-02-11T10:07:12+01:00 A variant upstream of HLA-DRB1 and multiple variants in MICA influence susceptibility to cervical cancer in a Swedish population Chen, Dan Hammer, Joanna Lindquist, David Idahl, Annika Gyllensten, Ulf 2014 application/pdf http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-238030 https://doi.org/10.1002/cam4.183 eng eng Uppsala universitet, Institutionen för immunologi, genetik och patologi Uppsala universitet, Science for Life Laboratory, SciLifeLab Umea Univ, Dept Radiat Sci, SE-90187 Umea, Sweden Umea Univ, Dept Clin Sci Obstet & Gynecol, SE-90187 Umea, Sweden Cancer Medicine, 2014, 3:1, s. 190-198 http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-238030 doi:10.1002/cam4.183 PMID 24403192 ISI:000348218200020 info:eu-repo/semantics/openAccess Cervical cancer cis-eQTL frameshift mutation HLA-DRB1 MICA Basic Medicine Medicinska och farmaceutiska grundvetenskaper Cancer and Oncology Cancer och onkologi Article in journal info:eu-repo/semantics/article text 2014 ftuppsalauniv https://doi.org/10.1002/cam4.183 2024-01-17T23:33:46Z In a genome-wide association study, we have previously identified and performed the initial replication of three novel susceptibility loci for cervical cancer: rs9272143 upstream of HLA-DRB1, rs2516448 adjacent to MHC class I polypeptide-related sequence A gene (MICA), and rs3117027 at HLA-DPB2. The risk allele T of rs2516448 is in perfect linkage disequilibrium with a frameshift mutation (A5.1) in MICA exon 5, which results in a truncated protein. To validate these associations in an independent study and extend our prior work to MICA exon 5, we genotyped the single-nucleotide polymorphisms at rs9272143, rs2516448, rs3117027 and the MICA exon 5 microsatellite in a nested case-control study of 961 cervical cancer patients (827 carcinoma in situ and 134 invasive carcinoma) and 1725 controls from northern Sweden. The C allele of rs9272143 conferred protection against cervical cancer (odds ratio [OR] = 0.73, 95% confidence interval [CI] = 0.65-0.82; P = 1.6 × 10(-7)), which is associated with higher expression level of HLA-DRB1, whereas the T allele of rs2516448 increased the susceptibility to cervical cancer (OR = 1.33, 95% CI = 1.19-1.49; P = 5.8 × 10(-7)), with the same association shown with MICA-A5.1. The direction and the magnitude of these associations were consistent with our previous findings. We also identified protective effects of the MICA-A4 (OR = 0.80, 95% CI = 0.68-0.94; P = 6.7 × 10(-3)) and MICA-A5 (OR = 0.60, 95% CI = 0.50-0.72; P = 3.0 × 10(-8)) alleles. The associations with these variants are unlikely to be driven by the nearby human leukocyte antigen (HLA) alleles. No association was observed between rs3117027 and risk of cervical cancer. Our results support the role of HLA-DRB1 and MICA in the pathogenesis of cervical cancer. Article in Journal/Newspaper Northern Sweden Uppsala University: Publications (DiVA) Cancer Medicine 3 1 190 198 |
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Open Polar |
collection |
Uppsala University: Publications (DiVA) |
op_collection_id |
ftuppsalauniv |
language |
English |
topic |
Cervical cancer cis-eQTL frameshift mutation HLA-DRB1 MICA Basic Medicine Medicinska och farmaceutiska grundvetenskaper Cancer and Oncology Cancer och onkologi |
spellingShingle |
Cervical cancer cis-eQTL frameshift mutation HLA-DRB1 MICA Basic Medicine Medicinska och farmaceutiska grundvetenskaper Cancer and Oncology Cancer och onkologi Chen, Dan Hammer, Joanna Lindquist, David Idahl, Annika Gyllensten, Ulf A variant upstream of HLA-DRB1 and multiple variants in MICA influence susceptibility to cervical cancer in a Swedish population |
topic_facet |
Cervical cancer cis-eQTL frameshift mutation HLA-DRB1 MICA Basic Medicine Medicinska och farmaceutiska grundvetenskaper Cancer and Oncology Cancer och onkologi |
description |
In a genome-wide association study, we have previously identified and performed the initial replication of three novel susceptibility loci for cervical cancer: rs9272143 upstream of HLA-DRB1, rs2516448 adjacent to MHC class I polypeptide-related sequence A gene (MICA), and rs3117027 at HLA-DPB2. The risk allele T of rs2516448 is in perfect linkage disequilibrium with a frameshift mutation (A5.1) in MICA exon 5, which results in a truncated protein. To validate these associations in an independent study and extend our prior work to MICA exon 5, we genotyped the single-nucleotide polymorphisms at rs9272143, rs2516448, rs3117027 and the MICA exon 5 microsatellite in a nested case-control study of 961 cervical cancer patients (827 carcinoma in situ and 134 invasive carcinoma) and 1725 controls from northern Sweden. The C allele of rs9272143 conferred protection against cervical cancer (odds ratio [OR] = 0.73, 95% confidence interval [CI] = 0.65-0.82; P = 1.6 × 10(-7)), which is associated with higher expression level of HLA-DRB1, whereas the T allele of rs2516448 increased the susceptibility to cervical cancer (OR = 1.33, 95% CI = 1.19-1.49; P = 5.8 × 10(-7)), with the same association shown with MICA-A5.1. The direction and the magnitude of these associations were consistent with our previous findings. We also identified protective effects of the MICA-A4 (OR = 0.80, 95% CI = 0.68-0.94; P = 6.7 × 10(-3)) and MICA-A5 (OR = 0.60, 95% CI = 0.50-0.72; P = 3.0 × 10(-8)) alleles. The associations with these variants are unlikely to be driven by the nearby human leukocyte antigen (HLA) alleles. No association was observed between rs3117027 and risk of cervical cancer. Our results support the role of HLA-DRB1 and MICA in the pathogenesis of cervical cancer. |
format |
Article in Journal/Newspaper |
author |
Chen, Dan Hammer, Joanna Lindquist, David Idahl, Annika Gyllensten, Ulf |
author_facet |
Chen, Dan Hammer, Joanna Lindquist, David Idahl, Annika Gyllensten, Ulf |
author_sort |
Chen, Dan |
title |
A variant upstream of HLA-DRB1 and multiple variants in MICA influence susceptibility to cervical cancer in a Swedish population |
title_short |
A variant upstream of HLA-DRB1 and multiple variants in MICA influence susceptibility to cervical cancer in a Swedish population |
title_full |
A variant upstream of HLA-DRB1 and multiple variants in MICA influence susceptibility to cervical cancer in a Swedish population |
title_fullStr |
A variant upstream of HLA-DRB1 and multiple variants in MICA influence susceptibility to cervical cancer in a Swedish population |
title_full_unstemmed |
A variant upstream of HLA-DRB1 and multiple variants in MICA influence susceptibility to cervical cancer in a Swedish population |
title_sort |
variant upstream of hla-drb1 and multiple variants in mica influence susceptibility to cervical cancer in a swedish population |
publisher |
Uppsala universitet, Institutionen för immunologi, genetik och patologi |
publishDate |
2014 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-238030 https://doi.org/10.1002/cam4.183 |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
Cancer Medicine, 2014, 3:1, s. 190-198 http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-238030 doi:10.1002/cam4.183 PMID 24403192 ISI:000348218200020 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1002/cam4.183 |
container_title |
Cancer Medicine |
container_volume |
3 |
container_issue |
1 |
container_start_page |
190 |
op_container_end_page |
198 |
_version_ |
1790605356259344384 |