PMID- 24403192
OWN - NLM
STAT- MEDLINE
DCOM- 20141125
LR  - 20211021
IS  - 2045-7634 (Electronic)
IS  - 2045-7634 (Print)
IS  - 2045-7634 (Linking)
VI  - 3
IP  - 1
DP  - 2014 Feb
TI  - A variant upstream of HLA-DRB1 and multiple variants in MICA influence 
      susceptibility to cervical cancer in a Swedish population.
PG  - 190-8
LID - 10.1002/cam4.183 [doi]
AB  - 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 x 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 x 
      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 x 10(-3)) and MICA-A5 (OR = 0.60, 95% CI = 0.50-0.72; P = 3.0 x 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.
CI  - (c) 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
FAU - Chen, Dan
AU  - Chen D
AD  - Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Science for 
      Life Laboratory Uppsala, Uppsala University, SE-751 85, Uppsala, Sweden.
FAU - Hammer, Joanna
AU  - Hammer J
FAU - Lindquist, David
AU  - Lindquist D
FAU - Idahl, Annika
AU  - Idahl A
FAU - Gyllensten, Ulf
AU  - Gyllensten U
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140107
PL  - United States
TA  - Cancer Med
JT  - Cancer medicine
JID - 101595310
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (MHC class I-related chain A)
SB  - IM
MH  - Adult
MH  - Female
MH  - *Genetic Association Studies
MH  - Genetic Predisposition to Disease
MH  - Genetics, Population
MH  - Genotype
MH  - HLA-DRB1 Chains/*genetics
MH  - Haplotypes
MH  - Histocompatibility Antigens Class I/*genetics
MH  - Humans
MH  - Polymorphism, Single Nucleotide
MH  - Sweden
MH  - Uterine Cervical Neoplasms/*genetics/pathology
PMC - PMC3930404
OTO - NOTNLM
OT  - Cervical cancer
OT  - HLA-DRB1
OT  - MICA
OT  - cis-eQTL
OT  - frameshift mutation
EDAT- 2014/01/10 06:00
MHDA- 2014/12/15 06:00
PMCR- 2014/02/01
CRDT- 2014/01/10 06:00
PHST- 2013/10/16 00:00 [received]
PHST- 2013/11/26 00:00 [revised]
PHST- 2013/11/29 00:00 [accepted]
PHST- 2014/01/10 06:00 [entrez]
PHST- 2014/01/10 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
PHST- 2014/02/01 00:00 [pmc-release]
AID - 10.1002/cam4.183 [doi]
PST - ppublish
SO  - Cancer Med. 2014 Feb;3(1):190-8. doi: 10.1002/cam4.183. Epub 2014 Jan 7.