Association Between Human Leukocyte Antigen (HLA)-DRB1 Genetic Polymorphism And Cervical Cancer

Human leukocyte antigen (HLA) complex, which is also called human major histocompatibility complex (MHC), is located with 6p21.31 region on the short arm of human chromosome 6.There are three types of HLA genes-I, II and III. The DR family which is a sublocus of Class II gene comprises a single A gene and up to 9 B genes (DRB1-9). The DRB1 gene is the extreme polymorphic gene of them. The HLA-DR antigens that are encoded by HLA-DR gene are expressed on the specialized cells, such as B cells, macrophages, and other antigen-presenting cells. T helper cells recognize the antigenic peptides bound to class II molecules through their antigen-specific T cell receptors (TCRs) thus help activate the immune responses. Cervical cancer (CC) is strongly associated with infection by human papillomavirus (HPV). However, not all women with HPV infection develop cervical cancer. HLA molecules, whose biological role is in discrimination of self from non-self antigens, may influence the progression of malignancy. Previous studies conducted in different populations regarding HLA class II polymorphisms and susceptibility to cervical cancer remains controversial but studies of Chinese populations have not shown. Objective: To explore the association between human leukocyte antigen (HLA)-DRB1 genetic polymorphism and cervical cancer, and further analyze the immunological mechanism of CC. Methods: The age of two groups was compared with t-test. The genotyping of HLA-DRB1 was done by polymerase chain reaction-sequence specific primers (PCR-SSP) in 43 patients and 58 healthy controls from Liaoning province. The allelic frequencies were calculated, and statistical differences between study groups were identified by use of the X~2 test. The magnitude of associations between alleles and the occurrence of CC was measured by odds ratios (ORs) and 95% confidence intervals (95%CI). Results: 1.The control group, of which HLA-DRB1 genotype frequencies accord with Hardy-Weinberg Equilibrium (P > 0.05), is the reliable representative of this population. 2.The distribution of HLA-DRB1 alleles and genotypes: (1) 12 alleles were observed in CC group. The range of allelic frequencies is from 2.33% to 29.07%. Among them the DRB1*15, *09, *07 allele are popular (the frequency of them is 29.07%, 11.63%, 11.63%, respectively), the DRB1*01, *10, *14 are rare (the frequency of them is 2.33% equally), DRB1*16 has not been examined.26 genotypes were observed and the frequencies range from 3.85% to 19.23%. (2) 13 alleles were observed in control group. The range of allelic frequencies is from 1.72% to 14.66%. Among them the DRB1*15, *09, *12 allele are popular (the frequency of them is 14.66%, 12.93%, 12.07%, respectively), the DRB1*10, *16, *01 are rare (the frequency of them is 1.72%, 2.59%, 3.45%, respectively). 40 genotypes were observed and the frequencies range from 2.5% to 7.5%. 3.The comparison of HLA-DRB1 allelic frequency: DRB1*15 allele in the CC group was significantly higher than that inthe healthy group (29.07% vs.14.66%, X2=6.231, P=0.013). It is positive correlated with cervical cancer (OR=2.387,95%CI=1.193-4.777). No significant difference of other allelic frequencies was observed between the two subjects. Conclusions: HLA-DRB1*15 allele increase the risk for cervical cancer in Liaoning province. The women taking DRB1*15 allele should do cervical cytologic examination for a period of time so as to detect and cure the pathological changes in the early stage. Understanding the association is necessary to describe the role that HLA molecules play in immune responses against viral infections and subsequent CC pathogenesis. On the other hand, it may also help to determine better approaches for prevention and treatment of cervical cancer through vaccination and immunotherapy.