HLA predisposition to human papillomavirus induced cervical neoplasia : population based studies from the Västerbotten county in northern Sweden

• Main Author: Ghaderi, Mehran
• Format: Doctoral or Postdoctoral Thesis
• Language: English
• Published: Institutionen för molekylär medicin / Department of Molecular Medicine 2001
• Subjects: Northern Sweden
• Online Access: http://hdl.handle.net/10616/40133

Infection with human papillomaviruses (HPV) types 16 and 18 is the major cause of cervical neoplasia. Although a high proportion of cervical cancers (CXCA) harbor HPV genomes, only a small number of women infected with high-risk papillomaviruses develop cervical tumors, suggesting that other environmental and/or genetic factors contribute to cervical carcinogenesis. Several studies have identified genes encoding human leukocyte antigens (HLA) associated with cervical intraepithelial neoplasia (CIN) and CXCA. Many genes encoding the products involved in immune responses are clustered within the human major histocompatibility complex (MHC) on the short arm of chromosome 6 (6p21.3). The human AMC extends over 3500 kilobases and comprises more than 200 genes with known and unknown functions The HLA class I genes encodes cell surface glycoproteins (HLA-A, -B, -C) that associates in the endoplasmic reticulum with beta32-microglubulin and peptides derived from endogenously processed antigens. HLA class II genes encode cell surface glycoproteins, which bind to peptides that originate mainly from exogenous antigens processed through the endosomal/lysosomal pathway. In addition to HLA class I and class II molecules, genes that encode the cytokines, tumor necrosis factor (TNF) alpha and beta are located in the class III region. The MHC class I chain related genes (MICA/B) located in the centromeric end of the HLA class I region, have recently been in focus for it can function as a ligand for gamma/delta T cells and NK cell receptors. MICA protein is mainly expressed by epithelial cells and its interaction with NK cells and gamma/delta T cells might have a role in the pathogenesis of CXCA. The aim of this thesis was to investigate the association of candidate HLA genes with CIN and CXCA. Several different genotyping methods were used to study the polymorphic HLA genes in two different patient groups. Patients and controls from a cohort of Västerbotten were included in this population-based study. Candidate genes in the HLA ...