title: Systematic investigation of contribution of genetic variation in the HLA-DP region to cervical cancer susceptibility.
abstract: Compared with the other human leukocyte antigen (HLA) genes, few studies have evaluated the role of HLA-DP genes in cervical cancer pathogenesis. A recent genome-wide association study (GWAS) in the Swedish population has identified a susceptibility locus for cervical cancer within the HLA-DP region. To further study this locus, we imputed classic HLA alleles using single-nucleotide polymorphism (SNP) data and analysed 449 genotyped and 3066 imputed SNPs in 1034 cervical cancer patients and 3948 controls. We confirmed that the strongest signal came from a SNP located at HLA-DPB2 [rs3117027, odds ratio (OR) = 1.29, 95% confidence interval (CI) = 1.16-1.43, P = 1.9 × 10(-6) for A allele] and that this effect is not driven by associations with classic HLA alleles. In silico analysis further revealed that this SNP is highly correlated with rs3129294 (D' = 1, r(2) = 0.95 in controls), which may have a putative regulatory function. We also identified an independent association at DPB1*0402, which conferred decreased risk of cervical cancer (OR = 0.75, 95% CI = 0.63-0.89, P = 7.0 × 10(-4)) and is independent of previously described associations with HLA-B*0702, DRB1*1501-DQB1*0602, and DRB1*1301-DQA1*0103-DQB1*0603. No association was found with the two SNPs (rs4282438 or rs9277952) that were recently identified within the HLA-DP region in a cervical cancer GWAS in the Chinese population. Our study provides the first systematic investigation of the association of genetic variants in the HLA-DP region with cervical cancer susceptibility and provides further insight into the contribution of polymorphisms in the HLA-DP region to risk of cervical cancer.
authors.affiliation: Department of Immunology, Genetics and Pathology, SciLifeLab Uppsala, Biomedical Center, Uppsala University, 75108 Uppsala, Sweden dan.chen@igp.uu.se simpledandan@gmail.com.
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Immunology, Genetics and Pathology, SciLifeLab Uppsala, Biomedical Center, Uppsala University, 75108 Uppsala, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Gyllensten
mesh_terms: D002278:Carcinoma in Situ / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006682:HLA-DP Antigens / Q000235:genetics*; D006801:Humans; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D013548:Sweden / Q000453:epidemiology; D018433:Twin Studies as Topic; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology
chemical_list: D006682:HLA-DP Antigens