학술논문
Common inherited variants of PDCD1, CD274 and HAVCR2 genes differentially modulate the risk and prognosis of adenocarcinoma and squamous cell carcinoma.
Document Type
Academic Journal
Author
Moksud N; Laboratory of Genetics and Epigenetics of Human Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114, Wrocław, Poland.; Wagner M; Laboratory of Genetics and Epigenetics of Human Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114, Wrocław, Poland.; Pawełczyk K; Lower Silesian Centre of Oncology, Pulmonology and Heamatology, Wrocław, Poland.; Porębska I; Department of Pulmonology and Lung Oncology, Wroclaw Medical University, Wrocław, Poland.; Muszczyńska-Bernhard B; Lower Silesian Centre of Oncology, Pulmonology and Heamatology, Wrocław, Poland.; Kowal A; Lower Silesian Centre of Oncology, Pulmonology and Heamatology, Wrocław, Poland.; Wiśniewski A; Laboratory of Immunogenetics and Tissue Immunology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.; Kosacka M; Department of Pulmonology and Lung Oncology, Wroclaw Medical University, Wrocław, Poland.; Kończak J; Department of Genetics and Cell Physiology, University of Wroclaw, Wrocław, Poland.; Karpiński P; Department of Genetics, Wroclaw Medical University, Wrocław, Poland.; Frydryk D; Department of Genetics and Cell Physiology, University of Wroclaw, Wrocław, Poland.; Andrzejczak A; Laboratory of Genetics and Epigenetics of Human Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114, Wrocław, Poland.; Karabon L; Laboratory of Genetics and Epigenetics of Human Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114, Wrocław, Poland.; Kuśnierczyk P; Laboratory of Immunogenetics and Tissue Immunology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.; Jasek M; Laboratory of Genetics and Epigenetics of Human Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114, Wrocław, Poland. monika.jasek@hirszfeld.pl.
Source
Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 7902060 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1335 (Electronic) Linking ISSN: 01715216 NLM ISO Abbreviation: J Cancer Res Clin Oncol Subsets: MEDLINE
Subject
Language
English
Abstract
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.
(© 2023. The Author(s).)
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.
(© 2023. The Author(s).)