HLA DRB allele polymorphisms and risk of cervical cancer associated with human papillomavirus infection: a population study in China

Objective: Persistent infection with high-risk human papillomavirus (HPV) is the main cause of cervical cancer. Environmental, behavioral, and ill-defined genetic factors have also been implicated in the pathogenesis of this disease. To determine whether human leukocyte antigen (HLA) DRB alleles are associated with cervical cancer and HPV infections in the Chinese population, HLA genotypes were examined in 69 cervical cancer patients and 201 controls. Materials and Methods: Polymorphisms in HLA-DRB genes were genotyped using oligoneucleotide arrays, and the magnitude of associations was determined by logistic regression analysis. Results: HLA-DRB1*13 (OR = 4.01 95% CI, 1.703 - 9.442) and HLA-DRB1*3(17) (OR = 2.661 95% CI, 1.267 - 5.558) were associated with an increased risk of cervical cancer, and DRB1*09012 (OR = 0.182, 95% CI, 0.079 - 0.418 and DRB1*1201 (OR = 0.35 95% CI, 0.142 - 0.863 were associated with a decreased risk. The risk associations of HPV infection were increased in women carrying the HLA-DRB1*09012 (OR = 1.924; 95% CI, 1.08 - 3.427) and DRB3(52)*0101 (OR = 7.527 95% CI, 0.909 - 62.347) alleles. Among cervical cancer patients, the risk associations differed between HPV positive and negative cases for several alleles; increased risk of cervical cancer was associated with DRB3 (52)*02/03 (OR, 12.794; 95% CI, 5.007 - 32.691) and DRB1*3(17) (OR = 3.48; 95% CI, 1.261 - 9.604), and decreased risk was associated with DRB1*09012 and DRB5(51)*01/02. Furthermore, HPV16-containing cervical cancer cases differed from non-HPV16 subjects in their positive association with DRB1*1501 (OR = 4.173; 95% CI, 1.065 - 16.356) and DRB5(51)*0101/0201, and their negative association with DRB4(53)*0101 (OR = 0.329; 95% CI,0.122 - 0.888). Conclusions: The present results provide further evidence that certain HLA class II allele polymorphisms are involved in the genetic susceptibility to cervical cancer and HPV infection in the Chinese population from an area with a high incidence of this neoplasia.

Cervical cancer; Human leukocyte antigens; Human papillomavirus.

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