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Updated: Dec 27, 2025
qKAT: Quantitative Semi-automated Typing of Killer-cell Immunoglobulin-like Receptor Genes
Published on: March 6, 2019
Analysis of Killer Immunoglobulin-Like Receptor Genes in Colorectal Cancer
Roberto Diaz-Peña1,2, Patricia Mondelo-Macía1, Antonio José Molina de la Torre3,4
1Liquid Biopsy Analysis Unit, Oncomet, Health Research Institute of Santiago (IDIS), 15706 Santiago de Compostela, Spain.
Abstract:
Natural killer cells (NK cells) play a major role in the immune response to cancer. An important element of NK target recognition is the binding of human leucocyte antigen (HLA) class I molecules by killer immunoglobulin-like receptors (KIRs). Colorectal carcinoma (CRC) is one of the most common types of inflammation-based cancer. The purpose of the present study was to investigate the presence of KIR genes and HLA class I and II alleles in 1074 CRC patients and 1272 controls. We imputed data from single-nucleotide polymorphism (SNP) Illumina OncoArray to identify associations at HLA (HLA-A, B, C, DPB1, DQA1, DQB1, and DRB1) and KIRs (HIBAG and KIR*IMP, respectively). For association analysis, we used PLINK (v1.9), the PyHLA software, and R version 3.4.0. Only three SNP markers showed suggestive associations (p < 10-3; rs16896742, rs28367832, and rs9277952). The frequency of KIR2DS3 was significantly increased in the CRC patients compared to healthy controls (p < 0.005). Our results suggest that the implication of NK cells in CRC may not act through allele combinations in KIR and HLA genes. Much larger studies in ethnically homogeneous populations are needed to rule out the possible role of allelic combinations in KIR and HLA genes in CRC risk.
Insights
Natural killer (NK) cells are crucial in cancer immunity. This study found no strong link between killer immunoglobulin-like receptor (KIR) and human leucocyte antigen (HLA) gene combinations and colorectal cancer (CRC) risk.
Area of Science:
- Immunology
- Genetics
- Oncology
Background:
- Natural killer (NK) cells are vital for anti-cancer immune responses.
- NK cell recognition involves killer immunoglobulin-like receptors (KIRs) binding human leucocyte antigen (HLA) class I molecules.
- Colorectal carcinoma (CRC) is a prevalent inflammation-associated cancer.
Purpose of the Study:
- To investigate the association between KIR genes, HLA class I and II alleles, and colorectal cancer (CRC).
- To explore the potential role of KIR-HLA interactions in CRC pathogenesis.
Main Methods:
- Genotyping of KIR and HLA alleles using imputed single-nucleotide polymorphism (SNP) data from Illumina OncoArray in 1074 CRC patients and 1272 controls.
- Statistical association analysis employing PLINK, PyHLA software, and R.
- Imputation of data for HLA (HLA-A, B, C, DPB1, DQA1, DQB1, DRB1) and KIR genes.
Main Results:
- Three SNP markers (rs16896742, rs28367832, rs9277952) showed suggestive associations with CRC (p < 10^-3).
- A significantly increased frequency of KIR2DS3 was observed in CRC patients compared to healthy controls (p < 0.005).
- No significant associations were found for combined KIR and HLA allele patterns in relation to CRC risk.
Conclusions:
- The current findings suggest that NK cell involvement in CRC may not be primarily driven by specific KIR and HLA allele combinations.
- Larger, ethnically homogeneous studies are required to definitively exclude the role of KIR-HLA allelic combinations in CRC susceptibility.
