Evaluation of the genetic diversity of KIR genes in patients with endometrial cancer

J Reprod Immunol. 2024 Mar:162:104217. doi: 10.1016/j.jri.2024.104217. Epub 2024 Feb 16.

Abstract

Endometrial cancer (EC) constitutes more than half of all genital cancers in women, with an increasing incidence in different countries. Natural killer cells (NK cells) are kinds of innate immune cells that are controlled by sets of receptors, such as killer cell Ig-like receptors (KIRs), which can inhibit or activate NK cells. In this study, we evaluated the diversity and genetic association of KIRs in confirmed cases of endometrial cancer compared to healthy controls. A total of 151 women with EC and 167 age/race-matched healthy controls were analyzed for KIR genes. Demographic and histopathologic data were gathered in questionnaires, and 16 KIR genes along with two variants of KIR2DS4 (KIR2DS4fl and KIR2DS4del), were genotyped by usingsequence specific primers-polymerase chain reaction (SSP-PCR) method. A comparison between cases and controls revealed that although there were not any significant differences in A haplotype associated genes and also the variants of KIR2DS4 (p >0.05), B haplotype associated genes such as KIR2DS2 and KIR2DL2 decreased significantly in EC patients in comparison with healthy controls (p=0.03 and p=0.01, respectively). Furthermore, we found that EC mostly developed in cases with the AA genotype; however, the carriers of Bx and C4T4 genotypes were less frequent in patients with EC. Our results revealed that KIR2DS2 and KIR2DL2, along with Bx and C4T4 genotypes, have a protective impact against developing endometrial cancer in Iranians.

Keywords: Endometrial cancer; Genetic variation; KIRs; NK cells.

MeSH terms

  • Endometrial Neoplasms* / genetics
  • Female
  • Gene Frequency
  • Genetic Variation
  • Genotype
  • Humans
  • Iran
  • Middle Eastern People*
  • Receptors, KIR* / genetics

Substances

  • KIR2DL2 protein, human
  • KIR2DS2 protein, human
  • KIR2DS4 protein, human
  • Receptors, KIR

Supplementary concepts

  • Iranian people