The Role of Non-classical and Chain-Related Human Leukocyte Antigen Polymorphisms in Laryngeal Squamous Cell Carcinoma

Abstract Background:Laryngeal cancer is one of the most common head and neck malignancies worldwide. Laryngeal squamous cell carcinoma (LSCC) is the major pathological subtype of laryngeal cancer. LSCC originates from the epidermal keratinocytes and is characterized by impaired keratinization. It has been shown that alterations of the expression of non-classical human leukocyte antigens (HLA) and the chain-related MIC molecules by malignant cells can lead to escape from the immune system control and certain allele variants may participate in immune editing and therefore be associated with modulation of cancer risk. The aim of the present study was to investigate the role of non-classical HLA class Ib and chain-related MIC polymorphisms, determined at the allelic level by next-generation sequencing (NGS), in patients from the Bulgarian population, diagnosed with LSCC. Materials and methods:In the present study DNA samples from 48 patients with LSCC were used. Data was compared to 68 healthy controls analysed in previous studies. HLA genotyping was performed by using the AlloSeq Tx17 early pooling protocol and the library preparation AlloSeq Tx17 kit (CareDx). Sequencing was performed on MiniSeq sequencing platform (Illumina) and HLA genotypes were assigned with the AlloSeq Assign analysis software v1.0.3 (CareDx) and the IPD-IMGT/HLA database 3.45.1.2. Results:The HLA disease association tests revealed a statistically significant predisposing association of HLA-F*01:01:02 (P=0.0103, OR=24.0194) with LSCC, while HLA-F*01:01:01 (P=8.21e-04, OR=0.0485) has a possible protective association. Additionally we observed several haplotypes with statistically significant protective and predisposing associations. The strongest association was observed for F*01:01:01-H*01:01:01 (P=0.0054, haplotype score=-2.7801). Conclusion:Our preliminary study suggests the involvement of HLA class Ib in cancer development and the possible role of the shown alleles as biomarkers of development of LSCC.