PMID- 18451182
OWN - NLM
STAT- MEDLINE
DCOM- 20080610
LR  - 20240312
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 68
IP  - 9
DP  - 2008 May 1
TI  - Comprehensive analysis of HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci and 
      squamous cell cervical cancer risk.
PG  - 3532-9
LID - 10.1158/0008-5472.CAN-07-6471 [doi]
AB  - Variation in human major histocompatibility genes may influence the risk of 
      squamous cell cervical cancer (SCC) by altering the efficiency of the 
      T-cell-mediated immune response to human papillomavirus (HPV) antigens. We used 
      high-resolution methods to genotype human leukocyte antigen (HLA) class I (A, B, 
      and Cw) and class II (DRB1 and DQB1) loci in 544 women with SCC and 542 controls. 
      Recognizing that HLA molecules are codominantly expressed, we focused on 
      co-occurring alleles. Among 137 allele combinations present at >5% in the case or 
      control groups, 36 were significantly associated with SCC risk. All but one of 
      the 30 combinations that increased risk included DQB1*0301, and 23 included 
      subsets of A*0201-B*4402-Cw*0501-DRB1*0401-DQB1*0301. Another combination, 
      B*4402-DRB1*1101-DQB1*0301, conferred a strong risk of SCC (odds ratio, 10.0; 95% 
      confidence interval, 3.0-33.3). Among the six combinations that conferred a 
      decreased risk of SCC, four included Cw*0701 or DQB1*02. Most multilocus results 
      were similar for SCC that contained HPV16; a notable exception was 
      A*0101-B*0801-Cw*0701-DRB1*0301-DQB1*0201 and its subsets, which were associated 
      with HPV16-positive SCC (odds ratio, 0.5; 95% confidence interval, 0.3-0.9). The 
      main multilocus associations were replicated in studies of cervical 
      adenocarcinoma and vulvar cancer. These data confirm that T helper and cytotoxic 
      T-cell responses are both important cofactors with HPV in cervical cancer 
      etiology and indicate that co-occurring HLA alleles across loci seem to be more 
      important than individual alleles. Thus, certain co-occurring alleles may be 
      markers of disease risk that have clinical value as biomarkers for targeted 
      screening or development of new therapies.
FAU - Madeleine, Margaret M
AU  - Madeleine MM
AD  - Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, WA 
      98109, USA. mmadelei@fhcrc.org
FAU - Johnson, Lisa G
AU  - Johnson LG
FAU - Smith, Anajane G
AU  - Smith AG
FAU - Hansen, John A
AU  - Hansen JA
FAU - Nisperos, Brenda B
AU  - Nisperos BB
FAU - Li, Sue
AU  - Li S
FAU - Zhao, Lue-Ping
AU  - Zhao LP
FAU - Daling, Janet R
AU  - Daling JR
FAU - Schwartz, Stephen M
AU  - Schwartz SM
FAU - Galloway, Denise A
AU  - Galloway DA
LA  - eng
GR  - R01 HL094260/HL/NHLBI NIH HHS/United States
GR  - R01 CA112512-02/CA/NCI NIH HHS/United States
GR  - R01CA112512/CA/NCI NIH HHS/United States
GR  - R01 CA112512-05/CA/NCI NIH HHS/United States
GR  - P01CA042792/CA/NCI NIH HHS/United States
GR  - P01 CA042792-19A1/CA/NCI NIH HHS/United States
GR  - R01 CA112512-01/CA/NCI NIH HHS/United States
GR  - P30 ES007033/ES/NIEHS NIH HHS/United States
GR  - P01ES07033/ES/NIEHS NIH HHS/United States
GR  - R01 CA112512-04/CA/NCI NIH HHS/United States
GR  - R01 CA112512/CA/NCI NIH HHS/United States
GR  - P30 ES007033-13/ES/NIEHS NIH HHS/United States
GR  - P01 CA042792/CA/NCI NIH HHS/United States
GR  - R01 CA112512-03/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-C Antigens)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQB1 antigen)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (HLA-DRB1*03:01 antigen)
RN  - 0 (HLA-DRB1*04:01 antigen)
RN  - 0 (Membrane Glycoproteins)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Age Distribution
MH  - Aged
MH  - Carcinoma, Squamous Cell/epidemiology/*genetics
MH  - Case-Control Studies
MH  - DNA Mutational Analysis
MH  - Female
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease
MH  - HLA-A Antigens/analysis/*genetics
MH  - HLA-B Antigens/analysis/*genetics
MH  - HLA-C Antigens/analysis/*genetics
MH  - HLA-DQ Antigens/analysis/*genetics
MH  - HLA-DQ beta-Chains
MH  - HLA-DR Antigens/analysis/*genetics
MH  - HLA-DRB1 Chains
MH  - Humans
MH  - Membrane Glycoproteins/analysis/*genetics
MH  - Middle Aged
MH  - Prevalence
MH  - Risk Factors
MH  - Sexual Partners
MH  - Smoking/epidemiology
MH  - Uterine Cervical Neoplasms/epidemiology/*genetics
PMC - PMC2662593
MID - NIHMS85424
EDAT- 2008/05/03 09:00
MHDA- 2008/06/11 09:00
PMCR- 2009/03/30
CRDT- 2008/05/03 09:00
PHST- 2008/05/03 09:00 [pubmed]
PHST- 2008/06/11 09:00 [medline]
PHST- 2008/05/03 09:00 [entrez]
PHST- 2009/03/30 00:00 [pmc-release]
AID - 68/9/3532 [pii]
AID - 10.1158/0008-5472.CAN-07-6471 [doi]
PST - ppublish
SO  - Cancer Res. 2008 May 1;68(9):3532-9. doi: 10.1158/0008-5472.CAN-07-6471.