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Inherited polymorphisms in the RNA-mediated interference machinery affect microRNA expression and lung cancer survival

BACKGROUND: MicroRNAs (miRs) have an important role in lung carcinogenesis and progression. Single-nucleotide polymorphisms (SNPs) in genes involved in miR biogenesis may affect miR expression in lung tissue and be associated with lung carcinogenesis and progression. METHODS: We analysed 12 SNPs in...

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Autores principales: Rotunno, M, Zhao, Y, Bergen, A W, Koshiol, J, Burdette, L, Rubagotti, M, Linnoila, R I, Marincola, F M, Bertazzi, P A, Pesatori, A C, Caporaso, N E, McShane, L M, Wang, E, Landi, M T
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3008605/
https://www.ncbi.nlm.nih.gov/pubmed/21102586
http://dx.doi.org/10.1038/sj.bjc.6605976
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author Rotunno, M
Zhao, Y
Bergen, A W
Koshiol, J
Burdette, L
Rubagotti, M
Linnoila, R I
Marincola, F M
Bertazzi, P A
Pesatori, A C
Caporaso, N E
McShane, L M
Wang, E
Landi, M T
author_facet Rotunno, M
Zhao, Y
Bergen, A W
Koshiol, J
Burdette, L
Rubagotti, M
Linnoila, R I
Marincola, F M
Bertazzi, P A
Pesatori, A C
Caporaso, N E
McShane, L M
Wang, E
Landi, M T
author_sort Rotunno, M
collection PubMed
description BACKGROUND: MicroRNAs (miRs) have an important role in lung carcinogenesis and progression. Single-nucleotide polymorphisms (SNPs) in genes involved in miR biogenesis may affect miR expression in lung tissue and be associated with lung carcinogenesis and progression. METHODS: We analysed 12 SNPs in POLR2A, RNASEN and DICER1 genes in 1984 cases and 2073 controls from the Environment And Genetics in Lung cancer Etiology (EAGLE) study. We investigated miR expression profiles in 165 lung adenocarcinoma (AD) and 125 squamous cell carcinoma tissue samples from the same population. We used logistic and Cox regression models to examine the association of individual genotypes and haplotypes with lung cancer risk and with lung cancer-specific survival, respectively. SNPs-miR expression associations in cases were assessed using two-sample t-tests and global permutation tests. RESULTS: A haplotype in RNASEN (Drosha) was significantly associated with shorter lung cancer survival (hazard ratio=1.86, 95% CI=1.19–2.92, P=0.007). In AD cases, a SNP within the same haplotype was associated with reduced RNASEN mRNA expression (P=0.013) and with miR expression changes (global P=0.007) of miRs known to be associated with cancer (e.g., let-7 family, miR-21, miR-25, miR-126 and miR15a). CONCLUSION: Inherited variation in the miR-processing machinery can affect miR expression levels and lung cancer-specific survival.
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spelling pubmed-30086052011-12-07 Inherited polymorphisms in the RNA-mediated interference machinery affect microRNA expression and lung cancer survival Rotunno, M Zhao, Y Bergen, A W Koshiol, J Burdette, L Rubagotti, M Linnoila, R I Marincola, F M Bertazzi, P A Pesatori, A C Caporaso, N E McShane, L M Wang, E Landi, M T Br J Cancer Genetics and Genomics BACKGROUND: MicroRNAs (miRs) have an important role in lung carcinogenesis and progression. Single-nucleotide polymorphisms (SNPs) in genes involved in miR biogenesis may affect miR expression in lung tissue and be associated with lung carcinogenesis and progression. METHODS: We analysed 12 SNPs in POLR2A, RNASEN and DICER1 genes in 1984 cases and 2073 controls from the Environment And Genetics in Lung cancer Etiology (EAGLE) study. We investigated miR expression profiles in 165 lung adenocarcinoma (AD) and 125 squamous cell carcinoma tissue samples from the same population. We used logistic and Cox regression models to examine the association of individual genotypes and haplotypes with lung cancer risk and with lung cancer-specific survival, respectively. SNPs-miR expression associations in cases were assessed using two-sample t-tests and global permutation tests. RESULTS: A haplotype in RNASEN (Drosha) was significantly associated with shorter lung cancer survival (hazard ratio=1.86, 95% CI=1.19–2.92, P=0.007). In AD cases, a SNP within the same haplotype was associated with reduced RNASEN mRNA expression (P=0.013) and with miR expression changes (global P=0.007) of miRs known to be associated with cancer (e.g., let-7 family, miR-21, miR-25, miR-126 and miR15a). CONCLUSION: Inherited variation in the miR-processing machinery can affect miR expression levels and lung cancer-specific survival. Nature Publishing Group 2010-12-07 2010-11-23 /pmc/articles/PMC3008605/ /pubmed/21102586 http://dx.doi.org/10.1038/sj.bjc.6605976 Text en Copyright © 2010 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Genetics and Genomics
Rotunno, M
Zhao, Y
Bergen, A W
Koshiol, J
Burdette, L
Rubagotti, M
Linnoila, R I
Marincola, F M
Bertazzi, P A
Pesatori, A C
Caporaso, N E
McShane, L M
Wang, E
Landi, M T
Inherited polymorphisms in the RNA-mediated interference machinery affect microRNA expression and lung cancer survival
title Inherited polymorphisms in the RNA-mediated interference machinery affect microRNA expression and lung cancer survival
title_full Inherited polymorphisms in the RNA-mediated interference machinery affect microRNA expression and lung cancer survival
title_fullStr Inherited polymorphisms in the RNA-mediated interference machinery affect microRNA expression and lung cancer survival
title_full_unstemmed Inherited polymorphisms in the RNA-mediated interference machinery affect microRNA expression and lung cancer survival
title_short Inherited polymorphisms in the RNA-mediated interference machinery affect microRNA expression and lung cancer survival
title_sort inherited polymorphisms in the rna-mediated interference machinery affect microrna expression and lung cancer survival
topic Genetics and Genomics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3008605/
https://www.ncbi.nlm.nih.gov/pubmed/21102586
http://dx.doi.org/10.1038/sj.bjc.6605976
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