Genetic variants in HLA-DP/DQ contribute to risk of cervical cancer: a two-stage study in Chinese women.

OBJECTIVE Human leukocyte antigens (HLA) play an important role in presenting virus antigens to immune cells that are responsible for the clearance of virus-infected cells and tumor cells. Herein, we evaluated whether genetic variants of HLA-DP and HLA-DQ are associated with cervical cancer risk. METHODS We genotyped four single nucleotide polymorphisms (SNPs) in HLA-DP (rs3077 and rs9277535) and HLA-DQ (rs2856718 and rs7453920) in a two-stage case-control study with a total of 2317 cervical cancer cases and 2109 cancer-free controls using TaqMan allelic discrimination assay. RESULTS We found consistently significant associations of HLA-DP rs3077 and rs9277535 with increased risks of cervical cancer (dominant genetic model: adjusted OR=1.51, 95% CI=1.32-1.71 for rs3077; adjusted OR=1.29, 95% CI=1.12-1.49 for rs9277535). When combining the effects of HLA-DP rs3077 and rs9277535, subjects carrying "≥1" variant alleles had a 1.55-fold increased risk of cervical cancer (95% CI=1.32-1.81), compared with those carrying "0" variant allele. And cervical cancer risk significantly increased with the increasing number of variant alleles of the two SNPs in a dose-dependent manner (P for trend=4.33×10(-10)). However, there were no significant associations for HLA-DQ rs2856718 and rs7453920 in our population. CONCLUSIONS These findings indicate that HLA-DP rs3077 and rs9277535 were candidate susceptibility markers for cervical cancer in Chinese females. Further validation studies with different ethnic background, biological function analyses and especially HPV typing together were needed.