Abstract 3812: Innate immunity in inflammatory breast cancer (IBC) patients: Clues from HLA profiling
Authors: Nicolas Batty, Pedro Cano, Pam Alizadeh, Sand Tin, Summer Jackson, Juanita Lara, Massimo Cristofanilli, James M. Reuben, Marcelo Fernandez-Vina
Journal: Cancer Research (2010)

Abstract Associations between HLA encoded factors with susceptibility and resistance to development of several common autoimmune disorders has been demonstrated in studies conducted more than 30 years ago. Subsequent studies have refined the mapping to these associations. In recent years it has been shown that HLA factors contribute to clearance of viruses including hepatitis C virus, Human Herpes Virus 8 or Epstein-Barr virus (EBV) and with decreased rates of progression to AIDS. EBV may also play a significant role in the pathogenesis of the Inflammatory Breast Cancer (IBC) accounting for some of the peculiar lymphangiogenic mechanism of growth and disease progression. We compared the distribution of alleles of HLA-A, -B, -C and DRB1 loci in 66 IBC patients of European ancestry with that of 776 ethnically matched healthy unrelated volunteers. HLA typing was performed utilizing PCR based assays combined with olugonucleotide hybridization and nucleotide sequencing. We observed that the alleles B*0801, Cw*0701 and DRB1*0301 were found with significantly lower frequencies in patients compared to the healthy donors (HD); these alleles were found in 7.6, 15.2 and 10.6 percent of the patients, compared with the phenotype frequencies of 22.5, 29.6 and 22.4 percent of the HD, respectively. The allele B*0801 had the lowest relative risk and had the statistically most significant difference (RR= 0.28, p= 0.004), while the alleles Cw*0701 (RR= 0.42, p= 0.012) and DRB1*0301 (RR= 0.41, p= 0.025) presented similar relative risks and significance. These HLA alleles are in tight linkage disequilibrium and form part of the most common HLA haplotype in European populations. Furthermore, the analyses of gene and haplotype distributions indicate that the significant decreases of the alleles at HLA-C and DRB1 loci, result from hitchhiking to the principal association of the allele B*0801 which may suggest a mechanism of protection from the risk of developing IBC from other associated infectious factors. Interestingly, the allele A*0101 that is found in linkage disequilibrium with B*0801 had a neutral effect (RR=0.97). The analysis also showed higher frequencies of the alleles Cw*0602 (RR=1.8, p=0.044) and DRB1*1301 (RR=1.8, p=0.044) and (RR=2.0, p=0.043) in IBC patients compared to controls; these alleles had small etiologic fractions (0.11 and 0.08). No significant associations were detected for other individual or groups of HLA alleles (KIR ligands and peptide binding supertypes). IBC is an aggressive and multifactorial disease. The possible association between the lack of B*0801 with predisposition to IBC may result from the previously reported memory responses to the immunodominant EBV epitopes which associates with HLA B8. These results contribute additional evidence for a role of EBV in the pathogenesis of IBC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3812.