Human leukocyte antigen class I and II alleles and risk of cervical neoplasia: results from a population-based study in Costa Rica.
To examine human leukocyte antigen (HLA) involvement in the development of all grades of cervical neoplasia, a nested case-control study of 10,077 women in Guanacaste, Costa Rica, was conducted. Participants had invasive cervical cancer, high-grade squamous intraepithelial lesions (HSILs; n=166), or low-grade squamous intraepithelial lesions (LSILs); were positive for human papillomavirus (HPV) with no evidence of cervical neoplasia (n=320); or were HPV negative with no evidence of cervical neoplasia but with a history of high-risk sexual behavior (n=173). Compared with women who were HPV negative, women with HLA-DRB1*1301 were associated with decreased risk for cancer/HSILs (odds ratio [OR], 0.4; 95% confidence interval [CI], 0.2-0.7) and for LSILs/HPV (OR, 0.6; 95% CI, 0.3-0.9). Women with both HLA-B*07 and HLA-DQB1*0302 had an 8.2-fold increased risk for cancer/HSILs (95% CI, 1.8-37.2) and a 5.3-fold increased risk for LSILs/HPV (95% CI, 1.2-23.7). These results support the hypothesis that multiple risk alleles are needed in order to increase risk for cervical neoplasia, but a single protective allele may be sufficient for protection.
Wang
S S
SS
Interdisciplinary Studies Section, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7234, USA. wangso@mail.nih.gov
Wheeler
C M
CM
Hildesheim
A
A
Schiffman
M
M
Herrero
R
R
Bratti
M C
MC
Sherman
M E
ME
Alfaro
M
M
Hutchinson
M L
ML
Morales
J
J
Lorincz
A
A
Burk
R D
RD
Carrington
M
M
Erlich
H A
HA
Apple
R J
RJ
D000483:Alleles; D016022:Case-Control Studies; D003364:Costa Rica / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D007962:Leukocytes / Q000276:immunology*; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II