Common inherited variants of PDCD1, CD274 and HAVCR2 genes differentially modulate the risk and prognosis of adenocarcinoma and squamous cell carcinoma

Background To investigate the association between single nucleotide polymorphisms (SNPs) of PDCD1 , CD274 , and HAVCR2 genes with the risk and outcomes of non-small cell lung cancer (NSCLC) subtypes: squamous cell lung cancer (LUSC) and lung adenocarcinoma (LUAD). Methods TaqMan SNP genotyping assay...

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Published in:Journal of cancer research and clinical oncology 2023-08, Vol.149 (9), p.6381-6390
Main Authors: Moksud, Nafeesa, Wagner, Marta, Pawełczyk, Konrad, Porębska, Irena, Muszczyńska-Bernhard, Beata, Kowal, Aneta, Wiśniewski, Andrzej, Kosacka, Monika, Kończak, Julia, Karpiński, Paweł, Frydryk, Dominik, Andrzejczak, Anna, Karabon, Lidia, Kuśnierczyk, Piotr, Jasek, Monika
Format: Article
Language:English
Subjects:
Adenocarcinoma
Adenocarcinoma - genetics
Adenocarcinoma of Lung
Alleles
B7-H1 Antigen - genetics
Cancer Research
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Squamous Cell - genetics
Gene polymorphism
Genetic Predisposition to Disease
Genotype & phenotype
Genotyping
Hematology
Hepatitis A Virus Cellular Receptor 2 - genetics
Humans
Internal Medicine
Lung cancer
Lung Neoplasms - genetics
Lung Neoplasms - pathology
Medical prognosis
Medicine
Medicine & Public Health
Non-small cell lung carcinoma
Oncology
PD-1 protein
PD-L1 protein
Polymorphism, Single Nucleotide
Prognosis
Programmed Cell Death 1 Receptor - genetics
Restriction fragment length polymorphism
Single-nucleotide polymorphism
Small cell lung carcinoma
Squamous cell carcinoma
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Summary:Background To investigate the association between single nucleotide polymorphisms (SNPs) of PDCD1 , CD274 , and HAVCR2 genes with the risk and outcomes of non-small cell lung cancer (NSCLC) subtypes: squamous cell lung cancer (LUSC) and lung adenocarcinoma (LUAD). Methods TaqMan SNP genotyping assays or polymerase chain reaction-restriction fragment length polymorphism methods were used to determine genotypes of: PDCD1: rs36084323, rs7421861, rs11568821, rs2227981, rs10204525; CD274 : rs822335, rs10815225, rs17718883, rs2297136, rs4742098, rs4143815; HAVCR2 : rs10057302, rs1036199. Among 383 NSCLC patients, 112 were diagnosed with LUAD and 116 with LUSC. The control group consisted of 433 unrelated, cancer-free subjects. Results A CC genotype of rs4143815 and GG genotype of rs4742098 were associated with two times higher risk of developing LUSC (CC vs. GG + GC, OR = 2.31; 95% CI = 1.32, 4.06; P  = 0.003; GG vs. AA + AG, OR = 2.26; 95% CI = 1.17, 4.36; P  = 0.016, respectively). Moreover, rs4143815 was an independent predictor of the age at diagnosis of LUAD. The carriers of C allele were diagnosed 4.81 years later (95% CI = 1.47, 8.15; P  = 0.006) than patients with the GG genotype. The rs10057302 CA genotype was an independent predictor of overall survival in LUSC (adjusted HR = 0.13; 95% CI = 0.02, 0.93; P  = 0.043). NSCLC carriers of rs11568821 T allele had almost double the risk of death (adjusted HR = 2.05; 95% CI = 1.28, 3.29; P  = 0.003) compared to carriers of CC genotype. Conclusions Our results provided additional evidence that SNPs of genes for PD-1, PD-L1 and TIM-3 differentially modulate the risk and prognosis of LUSC and LUAD.
ISSN:0171-5216
1432-1335
DOI:10.1007/s00432-023-04602-8