A variant upstream of HLA‐DRB1 and multiple variants in MICA influence susceptibility to cervical cancer in a Swedish population
Abstract 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 ‐ DRB 1 , rs2516448 adjacent to MHC class I polypeptide‐related sequence A gene ( MICA ), and rs3117027 a...
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crwiley:10.1002/cam4.183 2024-09-15T18:26:13+00:00 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 The Swedish Cancer Society (U.G.) The Medical Faculty of Uppsala University (D.C.) The Swedish Research Council (U.G.) 2014 http://dx.doi.org/10.1002/cam4.183 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fcam4.183 https://onlinelibrary.wiley.com/doi/pdf/10.1002/cam4.183 en eng Wiley http://creativecommons.org/licenses/by/3.0/ Cancer Medicine volume 3, issue 1, page 190-198 ISSN 2045-7634 2045-7634 journal-article 2014 crwiley https://doi.org/10.1002/cam4.183 2024-08-30T04:10:59Z Abstract 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 ‐ DRB 1 , rs2516448 adjacent to MHC class I polypeptide‐related sequence A gene ( MICA ), and rs3117027 at HLA ‐ DPB 2 . 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 ‐ DRB 1 , 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 ‐ DRB 1 and MICA in the pathogenesis of cervical cancer. Article in Journal/Newspaper Northern Sweden Wiley Online Library Cancer Medicine 3 1 190 198 |
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English |
description |
Abstract 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 ‐ DRB 1 , rs2516448 adjacent to MHC class I polypeptide‐related sequence A gene ( MICA ), and rs3117027 at HLA ‐ DPB 2 . 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 ‐ DRB 1 , 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 ‐ DRB 1 and MICA in the pathogenesis of cervical cancer. |
author2 |
The Swedish Cancer Society (U.G.) The Medical Faculty of Uppsala University (D.C.) The Swedish Research Council (U.G.) |
format |
Article in Journal/Newspaper |
author |
Chen, Dan Hammer, Joanna Lindquist, David Idahl, Annika Gyllensten, Ulf |
spellingShingle |
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 |
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 |
Wiley |
publishDate |
2014 |
url |
http://dx.doi.org/10.1002/cam4.183 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fcam4.183 https://onlinelibrary.wiley.com/doi/pdf/10.1002/cam4.183 |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_source |
Cancer Medicine volume 3, issue 1, page 190-198 ISSN 2045-7634 2045-7634 |
op_rights |
http://creativecommons.org/licenses/by/3.0/ |
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_ |
1810466670913781760 |