Polymorphisms of Antigen-Presenting Machinery Genes in Non-Small Cell Lung Cancer: Different Impact on Disease Risk and Clinical Parameters in Smokers and Never-Smokers
Lung cancer is strongly associated with cigarette smoking; nevertheless some never-smokers develop cancer. Immune eradication of cancer cells is dependent on polymorphisms of HLA class I molecules and antigen-processing machinery (APM) components. We have already published highly significant associa...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.664474/full |
| _version_ | 1818608249965903872 |
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| author | Andrzej Wiśniewski Maciej Sobczyński Konrad Pawełczyk Irena Porębska Monika Jasek Marta Wagner Wanda Niepiekło-Miniewska Aneta Kowal Joanna Dubis Natalia Jędruchniewicz Piotr Kuśnierczyk |
| author_facet | Andrzej Wiśniewski Maciej Sobczyński Konrad Pawełczyk Irena Porębska Monika Jasek Marta Wagner Wanda Niepiekło-Miniewska Aneta Kowal Joanna Dubis Natalia Jędruchniewicz Piotr Kuśnierczyk |
| author_sort | Andrzej Wiśniewski |
| collection | DOAJ |
| description | Lung cancer is strongly associated with cigarette smoking; nevertheless some never-smokers develop cancer. Immune eradication of cancer cells is dependent on polymorphisms of HLA class I molecules and antigen-processing machinery (APM) components. We have already published highly significant associations of single nucleotide polymorphisms (SNPs) of the ERAP1 gene with non-small cell lung cancer (NSCLC) in Chinese, but not in Polish populations. However, the smoking status of participants was not known in the previous study. Here, we compared the distribution of APM polymorphic variants in larger cohorts of Polish patients with NSCLC and controls, stratified according to their smoking status. We found significant but opposite associations in never-smokers and in smokers of all tested SNPs (rs26653, rs2287987, rs30187, and rs27044) but one (rs26618) in ERAP1. No significant associations were seen in other genes. Haplotype analysis indicated that the distribution of many ERAP1/2 haplotypes is opposite, depending on smoking status. Additionally, haplotypic combination of low activity ERAP1 and the lack of an active form of ERAP2 seems to favor the disease in never-smokers. We also revealed interesting associations of some APM polymorphisms with: age at diagnosis (ERAP1 rs26653), disease stage (ERAP1 rs27044, PSMB9 rs17587), overall survival (ERAP1 rs30187), and response to chemotherapy (ERAP1 rs27044). The results presented here may suggest the important role for ERAP1 in the anti-cancer response, which is different in smokers versus never-smokers, depending to some extent on the presence of ERAP2, and affecting NSCLC clinical course. |
| first_indexed | 2024-12-16T14:39:39Z |
| format | Article |
| id | doaj.art-19195e599fed4284b8bec4d3c7c94c86 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-16T14:39:39Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-19195e599fed4284b8bec4d3c7c94c862022-12-21T22:27:59ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-05-011210.3389/fimmu.2021.664474664474Polymorphisms of Antigen-Presenting Machinery Genes in Non-Small Cell Lung Cancer: Different Impact on Disease Risk and Clinical Parameters in Smokers and Never-SmokersAndrzej Wiśniewski0Maciej Sobczyński1Konrad Pawełczyk2Irena Porębska3Monika Jasek4Marta Wagner5Wanda Niepiekło-Miniewska6Aneta Kowal7Joanna Dubis8Natalia Jędruchniewicz9Piotr Kuśnierczyk10Laboratory of Immunogenetics and Tissue Immunology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, PolandDepartment of Bioinformatics and Genomics, Faculty of Biotechnology, University of Wrocław, Wrocław, PolandDepartment and Clinic of Thoracic Surgery, Wrocław Medical University, Wrocław, PolandDepartment of Pulmonology and Lung Oncology, Wrocław Medical University, Wrocław, PolandLaboratory of Immunogenetics and Tissue Immunology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, PolandLaboratory of Immunogenetics and Tissue Immunology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, PolandLaboratory of Immunogenetics and Tissue Immunology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, PolandDepartment of Pulmonology and Lung Oncology, Wrocław Medical University, Wrocław, PolandResearch and Development Centre, Regional Specialist Hospital in Wrocław, Wrocław, PolandResearch and Development Centre, Regional Specialist Hospital in Wrocław, Wrocław, PolandLaboratory of Immunogenetics and Tissue Immunology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, PolandLung cancer is strongly associated with cigarette smoking; nevertheless some never-smokers develop cancer. Immune eradication of cancer cells is dependent on polymorphisms of HLA class I molecules and antigen-processing machinery (APM) components. We have already published highly significant associations of single nucleotide polymorphisms (SNPs) of the ERAP1 gene with non-small cell lung cancer (NSCLC) in Chinese, but not in Polish populations. However, the smoking status of participants was not known in the previous study. Here, we compared the distribution of APM polymorphic variants in larger cohorts of Polish patients with NSCLC and controls, stratified according to their smoking status. We found significant but opposite associations in never-smokers and in smokers of all tested SNPs (rs26653, rs2287987, rs30187, and rs27044) but one (rs26618) in ERAP1. No significant associations were seen in other genes. Haplotype analysis indicated that the distribution of many ERAP1/2 haplotypes is opposite, depending on smoking status. Additionally, haplotypic combination of low activity ERAP1 and the lack of an active form of ERAP2 seems to favor the disease in never-smokers. We also revealed interesting associations of some APM polymorphisms with: age at diagnosis (ERAP1 rs26653), disease stage (ERAP1 rs27044, PSMB9 rs17587), overall survival (ERAP1 rs30187), and response to chemotherapy (ERAP1 rs27044). The results presented here may suggest the important role for ERAP1 in the anti-cancer response, which is different in smokers versus never-smokers, depending to some extent on the presence of ERAP2, and affecting NSCLC clinical course.https://www.frontiersin.org/articles/10.3389/fimmu.2021.664474/fullnon-small cell lung cancersmokers versus never-smokersantigen-processing machinerygeneticsERAP1ERAP2 |
| spellingShingle | Andrzej Wiśniewski Maciej Sobczyński Konrad Pawełczyk Irena Porębska Monika Jasek Marta Wagner Wanda Niepiekło-Miniewska Aneta Kowal Joanna Dubis Natalia Jędruchniewicz Piotr Kuśnierczyk Polymorphisms of Antigen-Presenting Machinery Genes in Non-Small Cell Lung Cancer: Different Impact on Disease Risk and Clinical Parameters in Smokers and Never-Smokers Frontiers in Immunology non-small cell lung cancer smokers versus never-smokers antigen-processing machinery genetics ERAP1 ERAP2 |
| title | Polymorphisms of Antigen-Presenting Machinery Genes in Non-Small Cell Lung Cancer: Different Impact on Disease Risk and Clinical Parameters in Smokers and Never-Smokers |
| title_full | Polymorphisms of Antigen-Presenting Machinery Genes in Non-Small Cell Lung Cancer: Different Impact on Disease Risk and Clinical Parameters in Smokers and Never-Smokers |
| title_fullStr | Polymorphisms of Antigen-Presenting Machinery Genes in Non-Small Cell Lung Cancer: Different Impact on Disease Risk and Clinical Parameters in Smokers and Never-Smokers |
| title_full_unstemmed | Polymorphisms of Antigen-Presenting Machinery Genes in Non-Small Cell Lung Cancer: Different Impact on Disease Risk and Clinical Parameters in Smokers and Never-Smokers |
| title_short | Polymorphisms of Antigen-Presenting Machinery Genes in Non-Small Cell Lung Cancer: Different Impact on Disease Risk and Clinical Parameters in Smokers and Never-Smokers |
| title_sort | polymorphisms of antigen presenting machinery genes in non small cell lung cancer different impact on disease risk and clinical parameters in smokers and never smokers |
| topic | non-small cell lung cancer smokers versus never-smokers antigen-processing machinery genetics ERAP1 ERAP2 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.664474/full |
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