51. High frequency of human leucocyte antigen (HLA) A2 and HLA-B7, -B44, -B15 and -DRB1–4 haplotypes in Swedish prostate cancer patients
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Sten Nilsson, Pavel Pisa, M. Ryberg, Emilia Andersson, Lars Egevad, Ulrika Harmenberg, Karl Mikael Kälkner, and Giuseppe Masucci
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Cancer Research ,Human leucocyte antigen ,biology ,business.industry ,Haplotype ,Immune escape ,Major histocompatibility complex ,medicine.disease ,Prostate cancer ,Oncology ,Tumour development ,Immunology ,biology.protein ,Medicine ,business - Abstract
14543 Background: Immune escape mechanisms depend on alterations in the expression of major histocompatibility complex (MHC) molecules and are known to play a crucial part in tumour development. We have previously presented high prevalence of the A2 allele in Scandinavia, which decreases with latitude in Europe and we noticed that prostate cancer mortality decreases among European countries in a similar way. We have furthermore characterized a group of prostate cancer patients with high frequency of HLA-A2 phenotype. Here we present prospectively the incidence of HLA-A2, homozygotes and haplotypes related to clinical parameters. Methods: Unbiased selected patients (n = 35) with localized prostate cancer, stage T1–3, NX-0, M0, eligible for curative full-dose radiotherapy, were analyzed for the genotypes HLA-A, -B, -C, and -DRB1 loci, by PCR/sequence-specific oligonucleotide hybridisation. Furthermore they have been compared to the frequencies of HLA alleles of healthy bone marrow donors in Sweden (based on 43 000 individuals). Results: The HLA-A2* phenotype frequency was 69% compared to the healthy Swedish population 58% (genotype frequency 39% vs. 35%). We also observed an increase in haplotypes compared to A2-B7 (14% vs 6%), A2-B44 (13% vs 6%), A2-B15 (14% vs 6%), A2-DRB1*04 (24% vs 8%). The ancestral haplotype HLA-A2, -B44, -DRB1*04 and HLA-A2, -B15, -DRB1*04 were expressed in 6% and 13% respectively in the patients group compared to the healthy Swedish population (2% and 3%). Conclusions: Our findings indicate that there is an unusual overrepresentation of the HLA-A2 allele and related haplotypes in prostate cancer patients. Further investigations are mandatory to establish if the negative prognostic correlation with HLA-A2 and the high frequent haplotypes is related to histological and clinical parameters as a result of disfunction of the immune system. No significant financial relationships to disclose.
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- 2006
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