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Genetic Variants Associated with Increased Risk of Malignant Pleural Mesothelioma: A Genome-Wide Association Study

Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, only 5–17% of those exposed to asbestos develop MPM, suggesting the involvement of other environmental and genetic risk factors. To identify the genetic risk factors that may co...

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Autores principales: Matullo, Giuseppe, Guarrera, Simonetta, Betti, Marta, Fiorito, Giovanni, Ferrante, Daniela, Voglino, Floriana, Cadby, Gemma, Di Gaetano, Cornelia, Rosa, Fabio, Russo, Alessia, Hirvonen, Ari, Casalone, Elisabetta, Tunesi, Sara, Padoan, Marina, Giordano, Mara, Aspesi, Anna, Casadio, Caterina, Ardissone, Francesco, Ruffini, Enrico, Betta, Pier Giacomo, Libener, Roberta, Guaschino, Roberto, Piccolini, Ezio, Neri, Monica, Musk, Arthur W. B., de Klerk, Nicholas H., Hui, Jennie, Beilby, John, James, Alan L., Creaney, Jenette, Robinson, Bruce W., Mukherjee, Sutapa, Palmer, Lyle J., Mirabelli, Dario, Ugolini, Donatella, Bonassi, Stefano, Magnani, Corrado, Dianzani, Irma
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3634031/
https://www.ncbi.nlm.nih.gov/pubmed/23626673
http://dx.doi.org/10.1371/journal.pone.0061253
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author Matullo, Giuseppe
Guarrera, Simonetta
Betti, Marta
Fiorito, Giovanni
Ferrante, Daniela
Voglino, Floriana
Cadby, Gemma
Di Gaetano, Cornelia
Rosa, Fabio
Russo, Alessia
Hirvonen, Ari
Casalone, Elisabetta
Tunesi, Sara
Padoan, Marina
Giordano, Mara
Aspesi, Anna
Casadio, Caterina
Ardissone, Francesco
Ruffini, Enrico
Betta, Pier Giacomo
Libener, Roberta
Guaschino, Roberto
Piccolini, Ezio
Neri, Monica
Musk, Arthur W. B.
de Klerk, Nicholas H.
Hui, Jennie
Beilby, John
James, Alan L.
Creaney, Jenette
Robinson, Bruce W.
Mukherjee, Sutapa
Palmer, Lyle J.
Mirabelli, Dario
Ugolini, Donatella
Bonassi, Stefano
Magnani, Corrado
Dianzani, Irma
author_facet Matullo, Giuseppe
Guarrera, Simonetta
Betti, Marta
Fiorito, Giovanni
Ferrante, Daniela
Voglino, Floriana
Cadby, Gemma
Di Gaetano, Cornelia
Rosa, Fabio
Russo, Alessia
Hirvonen, Ari
Casalone, Elisabetta
Tunesi, Sara
Padoan, Marina
Giordano, Mara
Aspesi, Anna
Casadio, Caterina
Ardissone, Francesco
Ruffini, Enrico
Betta, Pier Giacomo
Libener, Roberta
Guaschino, Roberto
Piccolini, Ezio
Neri, Monica
Musk, Arthur W. B.
de Klerk, Nicholas H.
Hui, Jennie
Beilby, John
James, Alan L.
Creaney, Jenette
Robinson, Bruce W.
Mukherjee, Sutapa
Palmer, Lyle J.
Mirabelli, Dario
Ugolini, Donatella
Bonassi, Stefano
Magnani, Corrado
Dianzani, Irma
author_sort Matullo, Giuseppe
collection PubMed
description Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, only 5–17% of those exposed to asbestos develop MPM, suggesting the involvement of other environmental and genetic risk factors. To identify the genetic risk factors that may contribute to the development of MPM, we conducted a genome-wide association study (GWAS; 370,000 genotyped SNPs, 5 million imputed SNPs) in Italy, among 407 MPM cases and 389 controls with a complete history of asbestos exposure. A replication study was also undertaken and included 428 MPM cases and 1269 controls from Australia. Although no single marker reached the genome-wide significance threshold, several associations were supported by haplotype-, chromosomal region-, gene- and gene-ontology process-based analyses. Most of these SNPs were located in regions reported to harbor aberrant alterations in mesothelioma (SLC7A14, THRB, CEBP350, ADAMTS2, ETV1, PVT1 and MMP14 genes), causing at most a 2–3-fold increase in MPM risk. The Australian replication study showed significant associations in five of these chromosomal regions (3q26.2, 4q32.1, 7p22.2, 14q11.2, 15q14). Multivariate analysis suggested an independent contribution of 10 genetic variants, with an Area Under the ROC Curve (AUC) of 0.76 when only exposure and covariates were included in the model, and of 0.86 when the genetic component was also included, with a substantial increase of asbestos exposure risk estimation (odds ratio, OR: 45.28, 95% confidence interval, CI: 21.52–95.28). These results showed that genetic risk factors may play an additional role in the development of MPM, and that these should be taken into account to better estimate individual MPM risk in individuals who have been exposed to asbestos.
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spelling pubmed-36340312013-04-26 Genetic Variants Associated with Increased Risk of Malignant Pleural Mesothelioma: A Genome-Wide Association Study Matullo, Giuseppe Guarrera, Simonetta Betti, Marta Fiorito, Giovanni Ferrante, Daniela Voglino, Floriana Cadby, Gemma Di Gaetano, Cornelia Rosa, Fabio Russo, Alessia Hirvonen, Ari Casalone, Elisabetta Tunesi, Sara Padoan, Marina Giordano, Mara Aspesi, Anna Casadio, Caterina Ardissone, Francesco Ruffini, Enrico Betta, Pier Giacomo Libener, Roberta Guaschino, Roberto Piccolini, Ezio Neri, Monica Musk, Arthur W. B. de Klerk, Nicholas H. Hui, Jennie Beilby, John James, Alan L. Creaney, Jenette Robinson, Bruce W. Mukherjee, Sutapa Palmer, Lyle J. Mirabelli, Dario Ugolini, Donatella Bonassi, Stefano Magnani, Corrado Dianzani, Irma PLoS One Research Article Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, only 5–17% of those exposed to asbestos develop MPM, suggesting the involvement of other environmental and genetic risk factors. To identify the genetic risk factors that may contribute to the development of MPM, we conducted a genome-wide association study (GWAS; 370,000 genotyped SNPs, 5 million imputed SNPs) in Italy, among 407 MPM cases and 389 controls with a complete history of asbestos exposure. A replication study was also undertaken and included 428 MPM cases and 1269 controls from Australia. Although no single marker reached the genome-wide significance threshold, several associations were supported by haplotype-, chromosomal region-, gene- and gene-ontology process-based analyses. Most of these SNPs were located in regions reported to harbor aberrant alterations in mesothelioma (SLC7A14, THRB, CEBP350, ADAMTS2, ETV1, PVT1 and MMP14 genes), causing at most a 2–3-fold increase in MPM risk. The Australian replication study showed significant associations in five of these chromosomal regions (3q26.2, 4q32.1, 7p22.2, 14q11.2, 15q14). Multivariate analysis suggested an independent contribution of 10 genetic variants, with an Area Under the ROC Curve (AUC) of 0.76 when only exposure and covariates were included in the model, and of 0.86 when the genetic component was also included, with a substantial increase of asbestos exposure risk estimation (odds ratio, OR: 45.28, 95% confidence interval, CI: 21.52–95.28). These results showed that genetic risk factors may play an additional role in the development of MPM, and that these should be taken into account to better estimate individual MPM risk in individuals who have been exposed to asbestos. Public Library of Science 2013-04-23 /pmc/articles/PMC3634031/ /pubmed/23626673 http://dx.doi.org/10.1371/journal.pone.0061253 Text en © 2013 Matullo et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Matullo, Giuseppe
Guarrera, Simonetta
Betti, Marta
Fiorito, Giovanni
Ferrante, Daniela
Voglino, Floriana
Cadby, Gemma
Di Gaetano, Cornelia
Rosa, Fabio
Russo, Alessia
Hirvonen, Ari
Casalone, Elisabetta
Tunesi, Sara
Padoan, Marina
Giordano, Mara
Aspesi, Anna
Casadio, Caterina
Ardissone, Francesco
Ruffini, Enrico
Betta, Pier Giacomo
Libener, Roberta
Guaschino, Roberto
Piccolini, Ezio
Neri, Monica
Musk, Arthur W. B.
de Klerk, Nicholas H.
Hui, Jennie
Beilby, John
James, Alan L.
Creaney, Jenette
Robinson, Bruce W.
Mukherjee, Sutapa
Palmer, Lyle J.
Mirabelli, Dario
Ugolini, Donatella
Bonassi, Stefano
Magnani, Corrado
Dianzani, Irma
Genetic Variants Associated with Increased Risk of Malignant Pleural Mesothelioma: A Genome-Wide Association Study
title Genetic Variants Associated with Increased Risk of Malignant Pleural Mesothelioma: A Genome-Wide Association Study
title_full Genetic Variants Associated with Increased Risk of Malignant Pleural Mesothelioma: A Genome-Wide Association Study
title_fullStr Genetic Variants Associated with Increased Risk of Malignant Pleural Mesothelioma: A Genome-Wide Association Study
title_full_unstemmed Genetic Variants Associated with Increased Risk of Malignant Pleural Mesothelioma: A Genome-Wide Association Study
title_short Genetic Variants Associated with Increased Risk of Malignant Pleural Mesothelioma: A Genome-Wide Association Study
title_sort genetic variants associated with increased risk of malignant pleural mesothelioma: a genome-wide association study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3634031/
https://www.ncbi.nlm.nih.gov/pubmed/23626673
http://dx.doi.org/10.1371/journal.pone.0061253
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