Killer cell immunoglobulin-like receptors (KIR) consists of activating and inhibitory genes are essential for natural killer cell education. To determine the association of KIRs with susceptibility to invasive Breast cancer (BC), genotyping of 16 KIRs was performed by sequence-specific primers-polymerase chain reaction in 226 confirmed cases of BC with defined estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) status and 226 healthy controls (CNs). We observed a lower frequency of 2DL1 and 2DS4del along with increased frequency of 2DS4fl in cases compared to CNs. Further analysis revealed a higher frequency of KIR2DL2, 2DS1, 2DS2,3DS1 in ER+ cases, 2DL2, 2DL5 in PR+ and 2DL1 in HER2+ cases compared to CNs. The detrimental role of KIR2DS4fl was observed in ER+ and PR+ cases whereas 2DS4del confers protection against ER+, PR+, and HER2+ cases. We noted the predisposing role of Bx genotype, KIR2DS1, 2DS2, 2DS5, 2DL2, 2DL5 for lymphatic invasion in ER+ cases along with a higher rate of lymph node metastasis (LNM) in carriers of Bx genotype and KIR2DS1 in ER+ cases. We suggest a link between B haplotype associated genes with the increased risk of lymphatic invasion and LNM, particularly in ER+ cases of BC.
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The study was financially supported by Shiraz University of Medical Sciences [grant number: 1396-01-01-16590] and partly by Shiraz Institute for Cancer Research [grant number: ICR-100-509]. Ethical approval of the research was confirmed by Medical Ethics Committee of Shiraz University of Medical Sciences [IR.SUMS.REC.1397.573]. The present study was part of a MSc thesis written by Marjan Hematian Larki.
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Hematian Larki, M., Barani, S., Talei, AR. et al. Diversity of KIRs in invasive breast cancer patients and healthy controls along with the clinical significance in ER/PR/HER2+ patients. Genes Immun 21, 380–389 (2020). https://doi.org/10.1038/s41435-020-00117-1