Association of killer cell immunoglobulin-like receptor gene 2DL1 and its HLA-C2 ligand with family history of cancer in oral squamous cell carcinoma

Abstract

Killer cell immunoglobulin-like receptors (KIR) are involved in regulating natural killer cell activation through recognition of their human leukocyte antigen (HLA) class I ligands. We conducted a case-control study with 169 oral squamous cell carcinoma (OSCC) patients and 177 healthy participants to study the genomic diversity of KIR and HLA loci and KIR gene expression in context of family history of cancer (FHC) in OSCC. Polymerase chain reaction (PCR) sequence-specific priming approach was used to type 16 KIR genes in individuals. SSP-real-time PCR was used for HLA class I ligand genotyping and real-time quantitative reverse transcriptase PCR was used to determine the expression of KIR gene. KIR2DL1(+)-HLA-C2(+) genotype was higher and positively associated with OSCC. Notably, all KIR2DL1(+)-HLA-C2(+) genotypes occurred exclusively in patients with FHC, showing a strong positive association of KIR2DL1(+)-HLA-C2(+) genotype with FHC. In addition, all younger age group patients (<55 years) with FHC were positive for KIR2DL1(+)-HLA-C2(+) genotype suggesting association of the genotype with early onset of disease. RNA transcript abundance of inhibitory KIR2DL1 in FHC patients, particularly of lower age groups (<45 and 45-54 years), supports the contention. Further, KIR2DL3(+)-HLA-C(+) genotype was negatively associated with OSCC. Our findings suggest KIR2DL1(+)-HLA-C2(+) genotype as heritable risk factor in OSCC predisposing to OSCC at younger age. Interestingly, KIR2DL3(+)-HLA-C(+) genotype was seen to be protective in OSCC. This study may be useful towards cancer surveillance and early detection of oral cancer in patients with FHC.

High-Resolution Genetic and Phenotypic Analysis of KIR2DL1 Alleles and Their Association with Pre-Eclampsia

“…The inhibitory receptor KIR2DL1 recognises HLA-C allotypes bearing a C2 epitope (C2 + HLA-C), defined by lysine at position 80. A number of disease associations studies have linked KIR2DL1 with outcome in cancer and transplantation (14) (15) (16). However, some of the strongest associations come from disorders of pregnancy.…”

Investigation of somatic single nucleotide variations in human endogenous retrovirus elements and their potential association with cancer

“…It regulates TGF-beta to drive breast carcinogenesis and facilitates the migration of cancer cells into bone [77]. KIR2DL1+-HLA-C2+ (human leukocyte antigen) genotype was found in oral cancer patients [78]. In Fig 2, multiple exons (Exon 1–5) of KIR2DL1, which overlap with MaLR/MST element seems associated with oral cancer.…”

Co‐evolution of the MHC class I and KIR gene families in rhesus macaques: ancestry and plasticity

“…One intriguing possibility is that this may be due to a highly efficient KIR repertoire on NK cells, which has been tailored to fight viral infections and has as a positive side‐effect the efficient recognition of determinants of malignant cells. In the case of humans, there are several association studies involving KIR and the occurrence of cancer or therapy regarding blood‐borne malignancies . For this reason, macaques may turn out to represent perfect models for studying and understanding cancer‐related resistance and treatment.…”