| Cervical cancer is one of the common neoplasias among women. Its motality and morbidity is the highest among all the female cancers in the developing countries. Multiple factors including age, sex life, pregnancy, endocrine and viral infection contribute to the occurrence of the cervical cancer. It is believed that human papillomaviruses (HPVs) play a critical role in the tumorigenesis of cervical cancer. As a matter of fact, HPV infections are responsible for the nearly 450,000 cervical cancers that occur each year throughout the world.As it is well-known that tumorigenesis of cervical cancer is a consecutive process of multiple stages and multiple factors, of which genetic background play an essential role per se.HLA comprises a family of genes within the human leukocyte antigen complex located on the short arm of chromosome (6p21.31) in humans. HLA molecules are highly polymorphic with nearly 1000 alleles. The peptide-binding region (PBR) of the HLA molecule utilizes the small pocket region on the surface to recognize the specific amino acids in the antigen peptide. Multiple antigen peptides can bind to a single HLA molecule via the interaction between the specific amino acids and the pocket. Since T cells can only recognize the HLA bound peptide antigens, all the potential T cell mediated immunity of an individual is determined by the carried set of HLA molecules. In another word, HLA molecules determine the individual immune response repertoire. Thus, the HLA molecules from different individuals possess the differential capacity to bind to the antigens from certain pathogen, thereby differential immune response and effect are induced as a result. Since the effective immune response is critical for the host to quarantine HPV infection and reverse HPV elicited damage, the prognosis of HPV infection of the individual might be determined by the specific immune response, which is signified by its genetic background. It is postulated that HLA complex is the major genetic determinant which is responsible formany aspects of cervical cancer progression including the prognosis of HPV infection, effective immune response, differential HPV clearance and ultimate cancer susceptibility.It has been verified by multiple studies that HLA molecules are related to the tumorigenesis of cervical cancer. However, most of studies focused on the correlation of type II genes and cervical cancer due to the effective application of HLA gene typing technique and relatively little work has been performed to identify the possible correlation of HLA genes and cervical cancer. This research bias for HLA Class II genes was driven by the availability of robust HLA Class II genotyping assays rather than scientific considerations. Since HLA-I molecules are important for the presentation of viral antigens and tumor antigens, we believe the systematic investigation of HLA-I gene and its alleles might provide a novel approach to further shed a light on cervical cancer susceptibility.The specimens were, collected from the fertile women in Wufeng autonomic district, a distant and isolated area, which is famous for the high incidence of cervical cancer in China. 42 samples of primary cervical cancer were collected as a result of 3-year screening (from March 2000 to March 2003) of 2162 fertile women. The ethnic principles were observed during the sampling procedure. All the 42 specimens were accompanied with the detailed clinical records and pathological diagnosis. As the control, 150 of normal non-related specimens from the same region with defined pathological diagnosis and similar distribution of ages were collected. The examination of HPV infection from cervical smears was routinely performed. HLA-A2 supertype alleles were genotyped by PCR/SSOP gene typing method. 2 ml of the peripheral blood was collected to extract genomic DNA by use of phenol/chloroform-based protocol. A pair of specific primers was used to amplify the 1-3 introns of the HLA-A locus, which includes the most polymorphic 2nd and 3rd intron. A single PCR amplification was... |
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