title: Human Leukocyte Antigen Class I and II Alleles and Cervical Adenocarcinoma.
abstract: BACKGROUND
  Associations between human leukocyte antigens (HLA) alleles and cervical cancer are largely representative of squamous cell carcinoma (SCC), the major histologic subtype. We evaluated the association between HLA class I (A, B, and C) and class II (DRB1 and DQB1) loci and risk of cervical adenocarcinoma (ADC), a less common but aggressive histologic subtype.
  
  
  METHODS
  We pooled data from the Eastern and Western US Cervical Cancer studies, and evaluated the association between individual alleles and allele combinations and ADC (n = 630 ADC; n = 775 controls). Risk estimates were calculated for 11 a priori (based on known associations with cervical cancer regardless of histologic type) and 38 non a priori common alleles, as odds ratios (OR) and 95% confidence intervals (CI), adjusted for age and study. In exploratory analysis, we compared the risk associations between subgroups with HPV16 or HPV18 DNA in ADC tumor tissues in the Western US study cases and controls.
  
  
  RESULTS
  Three of the a priori alleles were significantly associated with decreased risk of ADC [DRB1*13:01 (OR = 0.61; 95% CI: 0.41-0.93), DRB1*13:02 (OR = 0.49; 95% CI: 0.31-0.77), and DQB1*06:03 (OR = 0.64; 95% CI: 0.42-0.95)]; one was associated with increased risk [B*07:02 (OR = 1.39; 95% CI: 1.07-1.79)]. Among alleles not previously reported, DQB1*06:04 (OR = 0.46; 95% CI: 0.27-0.78) was associated with decreased risk of ADC and remained significant after correction for multiple comparisons, and C*07:02 (OR = 1.41; 95% CI: 1.09-1.81) was associated with increased risk. We did not observe a difference by histologic subtype. ADC was most strongly associated with increased risk with B*07:02/C*07:02 alleles (OR = 1.33; 95% CI: 1.01-1.76) and decreased risk with DRB1*13:02/DQB1*06:04 (OR = 0.41; 95% CI: 0.21-0.80).
  
  
  CONCLUSIONS
  RESULTS suggest that HLA allele associations with cervical ADC are similar to those for cervical SCC. An intriguing finding was the difference in risk associated with several alleles restricted to HPV16 or HPV18-related tumors, consistent with the hypothesis that HLA recognition is HPV type-specific.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute , Bethesda, MD , USA.
authors.forename: Mahboobeh
authors.initials: M
authors.lastname: Safaeian
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center , Seattle, WA , USA.
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Johnson
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute , Bethesda, MD , USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.affiliation: Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute and the City of Hope , Duarte, CA , USA.
authors.forename: Sophia S
authors.initials: SS
authors.lastname: Wang
authors.affiliation: School of Medicine, The University of New Mexico , Albuquerque, NM , USA.
authors.forename: Patti E
authors.initials: PE
authors.lastname: Gravitt
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center , Seattle, WA , USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Hansen
authors.affiliation: Cancer and Inflammation Program, Laboratory of Experimental Immunology, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research , Frederick, MD , USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center , Seattle, WA , USA ; Department of Epidemiology, University of Washington , Seattle, WA , USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Schwartz
authors.affiliation: Cancer and Inflammation Program, Laboratory of Experimental Immunology, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research , Frederick, MD , USA.
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute , Bethesda, MD , USA.
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center , Seattle, WA , USA ; Department of Epidemiology, University of Washington , Seattle, WA , USA.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Madeleine
keywords: HLA class I; HLA class II; HPV; cervical adenocarcinoma; host genetics