PMID- 36241658
OWN - NLM
STAT- MEDLINE
DCOM- 20221018
LR  - 20230105
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 12
IP  - 1
DP  - 2022 Oct 14
TI  - KIR-HLA gene diversities and susceptibility to lung cancer.
PG  - 17237
LID - 10.1038/s41598-022-21062-1 [doi]
LID - 17237
AB  - Killer-cell immunoglobulin-like receptors (KIR) are essential for acquiring 
      natural killer (NK) cell effector function, which is modulated by a balance 
      between the net input of signals derived from inhibitory and activating receptors 
      through engagement by human leukocyte antigen (HLA) class I ligands. KIR and HLA 
      loci are polygenic and polymorphic and exhibit substantial variation between 
      individuals and populations. We attempted to investigate the contribution of KIR 
      complex and HLA class I ligands to the genetic predisposition to lung cancer in 
      the native population of southern Iran. We genotyped 16 KIR genes for a total of 
      232 patients with lung cancer and 448 healthy controls (HC), among which 85 
      patients and 178 HCs were taken into account for evaluating combined KIR-HLA 
      associations. KIR2DL2 and 2DS2 were increased significantly in patients than in 
      controls, individually (OR 1.63, and OR 1.42, respectively) and in combination 
      with HLA-C1 ligands (OR 1.99, and OR 1.93, respectively). KIR3DS1 (OR 0.67) and 
      2DS1 (OR 0.69) were more likely presented in controls in the absence of their 
      relative ligands. The incidence of CxTx subset was increased in lung cancer 
      patients (OR 1.83), and disease risk strikingly increased by more than fivefold 
      among genotype ID19 carriers (a CxTx genotype that carries 2DL2 in the absence of 
      2DS2, OR 5.92). We found that genotypes with iKIRs > aKIRs (OR 1.67) were more 
      frequently presented in lung cancer patients. Additionally, patients with lung 
      cancer were more likely to carry the combination of CxTx/2DS2 compared to 
      controls (OR 2.04), and iKIRs > aKIRs genotypes in the presence of 2DL2 (OR 2.05) 
      increased the likelihood of lung cancer development. Here we report new 
      susceptibility factors and the contribution of KIR and HLA-I encoding genes to 
      lung cancer risk, highlighting an array of genetic effects and disease setting 
      which regulates NK cell responsiveness. Our results suggest that inherited KIR 
      genes and HLA-I ligands specifying the educational state of NK cells can modify 
      lung cancer risk.
CI  - (c) 2022. The Author(s).
FAU - Hematian Larki, Marjan
AU  - Hematian Larki M
AUID- ORCID: 0000-0002-0246-5050
AD  - Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of 
      Medical Sciences, Shiraz, Iran.
FAU - Ashouri, Elham
AU  - Ashouri E
AD  - Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of 
      Medical Sciences, Shiraz, Iran.
FAU - Barani, Shaghik
AU  - Barani S
AD  - Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of 
      Medical Sciences, Shiraz, Iran.
FAU - Ghayumi, Seiyed Mohammad Ali
AU  - Ghayumi SMA
AD  - Department of Internal Medicine, School of Medicine, Shiraz University of Medical 
      Sciences, Shiraz, Iran.
FAU - Ghaderi, Abbas
AU  - Ghaderi A
AUID- ORCID: 0000-0003-0849-3375
AD  - Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of 
      Medical Sciences, Shiraz, Iran. ghaderia@sums.ac.ir.
AD  - Department of Immunology, School of Medicine, Shiraz University of Medical 
      Sciences, Shiraz, Iran. ghaderia@sums.ac.ir.
FAU - Rajalingam, Raja
AU  - Rajalingam R
AUID- ORCID: 0000-0001-8821-7877
AD  - Immunogenetics and Transplantation Laboratory, Department of Surgery, University 
      of California San Francisco, San Francisco, CA, USA. Rajalingam.Raja@ucsf.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221014
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Immunoglobulins)
RN  - 0 (Ligands)
RN  - 0 (Receptors, KIR)
SB  - IM
MH  - Gene Frequency
MH  - Genotype
MH  - HLA Antigens/genetics
MH  - Histocompatibility Antigens Class I/genetics
MH  - Humans
MH  - Immunoglobulins/genetics
MH  - Ligands
MH  - *Lung Neoplasms/genetics
MH  - *Receptors, KIR/genetics
PMC - PMC9568660
COIS- The authors declare no competing interests.
EDAT- 2022/10/15 06:00
MHDA- 2022/10/19 06:00
PMCR- 2022/10/14
CRDT- 2022/10/14 23:18
PHST- 2022/06/13 00:00 [received]
PHST- 2022/09/22 00:00 [accepted]
PHST- 2022/10/14 23:18 [entrez]
PHST- 2022/10/15 06:00 [pubmed]
PHST- 2022/10/19 06:00 [medline]
PHST- 2022/10/14 00:00 [pmc-release]
AID - 10.1038/s41598-022-21062-1 [pii]
AID - 21062 [pii]
AID - 10.1038/s41598-022-21062-1 [doi]
PST - epublish
SO  - Sci Rep. 2022 Oct 14;12(1):17237. doi: 10.1038/s41598-022-21062-1.