Distribution of HLA Class II and MHC Class III Alleles in Gastric Cancer

Lyrakos, Nikolaos (2001) Distribution of HLA Class II and MHC Class III Alleles in Gastric Cancer. MSc(R) thesis, University of Glasgow.

Abstract

The progression from normal to neoplastic cells takes place over an undefined period under the combined influence of several factors, including genetic susceptibility. The MHC system (HLA in humans) is composed of genes that control a variety of immune functions and influence the susceptibility for more than 40 diseases, including cancer. This study was to investigate the relationship among cytokine related genetic loci on chromosome 6 that might be involved in Barrett's oesophagus and in gastric cancer that involves a major "environmental factor" Helicobacter Pylori infection. The genetic loci investigated were the HLA-DQB1 locus, the HSP-70-2 locus and D6S273 marker and compared with TNFa 1-14 microsatellites, on chromosome 6, in region 2, band 1, sub-band 3. The subjects taking part in this investigation were patients with Barrett's oesophagus, patients with gastric cancer and a cancer free population, all originated from the West of Scotland. The protocols used were PCR based and radioactive PCR microsatellite analysis. performed in order to refine the genetic contribution of the three loci that were investigated, in gastric cancer and in Barrett's oesophagus conditions and to fine map the relationship of the TNF locus with adjacent genetic loci that span from the HLA class-II region to HLA-B locus. The results obtained suggest that there is a significant difference in genotype and allelotype distribution in certain loci. Significant associations were discovered in the DQbeta1 locus for the DQ3 serotype (gastric cancer Vs controls; P = 0.0421), in the HSP 70-2 locus genotype 1 * 2 (malignant Barrett's Vs controls; P = 0.0194), in the D6S273 locus genotype 132-134 (malignant Barrett's Vs controls; P = 0.0337) and the allelotype (serotype) DQ6 (total Barrett's population Vs controls; P= 0.0252). Also there are significant differences in allelotype distribution among certain loci where significant association was discovered between the DQ?1 locus and the HSP 70-2 locus (DQ 2 - HSP (936bp) alleles in gastric population Vs controls; P= 0.0487). Additionally, there is not a defined difference in genotype-allelotype distribution and no significant association was discovered among the three loci tested compared with the TNFa 1-14 microsatellites. Our study leads to the conclusion that the HLA-DQbeta1, HSP-70-2 and D6S273 loci are associated with gastric cancer and Barrett's oesophagus and that the HLA-DQbeta1 and the HSP-70-2 loci are in linkage with each other for the genotype (DQ2-HSP (936bp). In addition none of the three loci tested are in close linkage with the TNF locus. Encouraging results were obtained, and there could be a possibility that new immunogenetic therapeutic procedures for Barrett's oesophagus and gastric cancer could be based on these specific immunogenetic targets (i.e. HLA-DQbeta1, HSP-70-2, and D6S273), their protein products and relative cytokines.

• Item Type: Thesis (MSc(R))
• Qualification Level: Masters
• Additional Information: Adviser: Grant Gallagher
• Keywords: Medicine, Oncology
• Date of Award: 2001
• Depositing User: Enlighten Team
• Unique ID: glathesis:2001-75724
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 19 Dec 2019 09:15
• Last Modified: 19 Dec 2019 09:15
• URI: https://theses.gla.ac.uk/id/eprint/75724