Systematic investigation of contribution of genetic variation in the HLA-DP region to cervical cancer susceptibility

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 x 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 x 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.