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Programmed Death Ligand 2 Gene Polymorphisms Are Associated With Lung Adenocarcinoma Risk in Female Never-Smokers

OBJECTIVES: Lung cancer in never-smokers is a distinct disease associated with a different genomic landscape, pathogenesis, risk factors, and immune checkpoint inhibitor responses compared to those observed in smokers. This study aimed to identify novel single nucleotide polymorphisms (SNPs) of prog...

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Autores principales: Liang, Sheng-Kai, Chien, Li-Hsin, Chang, Gee-Chen, Tsai, Ying-Huang, Su, Wu-Chou, Chen, Yuh-Min, Huang, Ming-Shyan, Lin, Hsien-Chih, Fang, Wen-Tsen, Hung, Hsiao-Han, Jiang, Shih-Sheng, Chen, Chih-Yi, Chen, Kuan-Yu, Chang, I-Shou, Hsiung, Chao A., Chen, Chien-Jen, Yang, Pan-Chyr
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497977/
https://www.ncbi.nlm.nih.gov/pubmed/34631591
http://dx.doi.org/10.3389/fonc.2021.753788
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author Liang, Sheng-Kai
Chien, Li-Hsin
Chang, Gee-Chen
Tsai, Ying-Huang
Su, Wu-Chou
Chen, Yuh-Min
Huang, Ming-Shyan
Lin, Hsien-Chih
Fang, Wen-Tsen
Hung, Hsiao-Han
Jiang, Shih-Sheng
Chen, Chih-Yi
Chen, Kuan-Yu
Chang, I-Shou
Hsiung, Chao A.
Chen, Chien-Jen
Yang, Pan-Chyr
author_facet Liang, Sheng-Kai
Chien, Li-Hsin
Chang, Gee-Chen
Tsai, Ying-Huang
Su, Wu-Chou
Chen, Yuh-Min
Huang, Ming-Shyan
Lin, Hsien-Chih
Fang, Wen-Tsen
Hung, Hsiao-Han
Jiang, Shih-Sheng
Chen, Chih-Yi
Chen, Kuan-Yu
Chang, I-Shou
Hsiung, Chao A.
Chen, Chien-Jen
Yang, Pan-Chyr
author_sort Liang, Sheng-Kai
collection PubMed
description OBJECTIVES: Lung cancer in never-smokers is a distinct disease associated with a different genomic landscape, pathogenesis, risk factors, and immune checkpoint inhibitor responses compared to those observed in smokers. This study aimed to identify novel single nucleotide polymorphisms (SNPs) of programmed death-1 (encoded by PDCD1) and its ligands, programmed death ligand 1 (CD274) and 2 (PDCD1LG2), associated with lung cancer risk in never-smoking women. MATERIALS AND METHODS: During September 2002 and July 2012, we enrolled never-smoking female patients with lung adenocarcinoma (LUAD) (n=1153) and healthy women (n=1022) from six tertiary hospitals in Taiwan. SNP data were obtained and analyzed from the genome-wide association study dataset and through an imputation method. The expression quantitative trait loci (eQTL) analysis was performed in both tumor and non-tumor tissues for the correlation between genetic expression and identified SNPs. RESULTS: A total of 12 PDCD1LG2 SNPs related to LUAD risk were identified in never-smoking women, including rs2381282, rs4742103, rs4237162, rs4742104, rs12237624, rs78096119, rs6476988, rs7857315, rs10975178, rs7854413, rs56001683, and rs7858319. Among them, six tagged PDCD1LG2 SNPs rs2381282, rs4742103, rs4237162, rs4742104, rs78096119, and rs56001683 were significantly associated with LUAD risk. Specifically, two PDCD1LG2 SNPs, rs12237624 and rs78096119, were associated with previous pulmonary tuberculosis infection in relation to LUAD susceptibility. Through an eQTL assay, we found that rs2381282 (p < 0.001), rs12237624 (p = 0.019), and rs78096119 (p = 0.019) were associated with the expression levels of programed death ligand 2. CONCLUSIONS: Novel SNPs of programed death ligand 2 associated with lung adenocarcinoma risk were identified. Among them, two SNPs were associated with pulmonary tuberculosis infection in relation to lung adenocarcinoma susceptibility. These SNPs may help to stratify high-risk populations of never-smokers during lung cancer screening.
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spelling pubmed-84979772021-10-09 Programmed Death Ligand 2 Gene Polymorphisms Are Associated With Lung Adenocarcinoma Risk in Female Never-Smokers Liang, Sheng-Kai Chien, Li-Hsin Chang, Gee-Chen Tsai, Ying-Huang Su, Wu-Chou Chen, Yuh-Min Huang, Ming-Shyan Lin, Hsien-Chih Fang, Wen-Tsen Hung, Hsiao-Han Jiang, Shih-Sheng Chen, Chih-Yi Chen, Kuan-Yu Chang, I-Shou Hsiung, Chao A. Chen, Chien-Jen Yang, Pan-Chyr Front Oncol Oncology OBJECTIVES: Lung cancer in never-smokers is a distinct disease associated with a different genomic landscape, pathogenesis, risk factors, and immune checkpoint inhibitor responses compared to those observed in smokers. This study aimed to identify novel single nucleotide polymorphisms (SNPs) of programmed death-1 (encoded by PDCD1) and its ligands, programmed death ligand 1 (CD274) and 2 (PDCD1LG2), associated with lung cancer risk in never-smoking women. MATERIALS AND METHODS: During September 2002 and July 2012, we enrolled never-smoking female patients with lung adenocarcinoma (LUAD) (n=1153) and healthy women (n=1022) from six tertiary hospitals in Taiwan. SNP data were obtained and analyzed from the genome-wide association study dataset and through an imputation method. The expression quantitative trait loci (eQTL) analysis was performed in both tumor and non-tumor tissues for the correlation between genetic expression and identified SNPs. RESULTS: A total of 12 PDCD1LG2 SNPs related to LUAD risk were identified in never-smoking women, including rs2381282, rs4742103, rs4237162, rs4742104, rs12237624, rs78096119, rs6476988, rs7857315, rs10975178, rs7854413, rs56001683, and rs7858319. Among them, six tagged PDCD1LG2 SNPs rs2381282, rs4742103, rs4237162, rs4742104, rs78096119, and rs56001683 were significantly associated with LUAD risk. Specifically, two PDCD1LG2 SNPs, rs12237624 and rs78096119, were associated with previous pulmonary tuberculosis infection in relation to LUAD susceptibility. Through an eQTL assay, we found that rs2381282 (p < 0.001), rs12237624 (p = 0.019), and rs78096119 (p = 0.019) were associated with the expression levels of programed death ligand 2. CONCLUSIONS: Novel SNPs of programed death ligand 2 associated with lung adenocarcinoma risk were identified. Among them, two SNPs were associated with pulmonary tuberculosis infection in relation to lung adenocarcinoma susceptibility. These SNPs may help to stratify high-risk populations of never-smokers during lung cancer screening. Frontiers Media S.A. 2021-09-24 /pmc/articles/PMC8497977/ /pubmed/34631591 http://dx.doi.org/10.3389/fonc.2021.753788 Text en Copyright © 2021 Liang, Chien, Chang, Tsai, Su, Chen, Huang, Lin, Fang, Hung, Jiang, Chen, Chen, Chang, Hsiung, Chen, Yang and the GELAC Study Group https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Liang, Sheng-Kai
Chien, Li-Hsin
Chang, Gee-Chen
Tsai, Ying-Huang
Su, Wu-Chou
Chen, Yuh-Min
Huang, Ming-Shyan
Lin, Hsien-Chih
Fang, Wen-Tsen
Hung, Hsiao-Han
Jiang, Shih-Sheng
Chen, Chih-Yi
Chen, Kuan-Yu
Chang, I-Shou
Hsiung, Chao A.
Chen, Chien-Jen
Yang, Pan-Chyr
Programmed Death Ligand 2 Gene Polymorphisms Are Associated With Lung Adenocarcinoma Risk in Female Never-Smokers
title Programmed Death Ligand 2 Gene Polymorphisms Are Associated With Lung Adenocarcinoma Risk in Female Never-Smokers
title_full Programmed Death Ligand 2 Gene Polymorphisms Are Associated With Lung Adenocarcinoma Risk in Female Never-Smokers
title_fullStr Programmed Death Ligand 2 Gene Polymorphisms Are Associated With Lung Adenocarcinoma Risk in Female Never-Smokers
title_full_unstemmed Programmed Death Ligand 2 Gene Polymorphisms Are Associated With Lung Adenocarcinoma Risk in Female Never-Smokers
title_short Programmed Death Ligand 2 Gene Polymorphisms Are Associated With Lung Adenocarcinoma Risk in Female Never-Smokers
title_sort programmed death ligand 2 gene polymorphisms are associated with lung adenocarcinoma risk in female never-smokers
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497977/
https://www.ncbi.nlm.nih.gov/pubmed/34631591
http://dx.doi.org/10.3389/fonc.2021.753788
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