作者
Giuseppe Matullo, Simonetta Guarrera, Marta Betti, Giovanni Fiorito, Daniela Ferrante, Floriana Voglino, Gemma Cadby, Cornelia Di Gaetano, Fabio Rosa, Alessia Russo, Ari Hirvonen, Elisabetta Casalone, Sara Tunesi, Marina Padoan, Mara Giordano, Anna Aspesi, Caterina Casadio, Francesco Ardissone, Enrico Ruffini, Pier Giacomo Betta, Roberta Libener, Roberto Guaschino, Ezio Piccolini, Monica Neri, Arthur WB Musk, Nicholas H de Klerk, Jennie Hui, John Beilby, Alan L James, Jenette Creaney, Bruce W Robinson, Sutapa Mukherjee, Lyle J Palmer, Dario Mirabelli, Donatella Ugolini, Stefano Bonassi, Corrado Magnani, Irma Dianzani
发表日期
2013/4/23
期刊
PloS one
卷号
8
期号
4
页码范围
e61253
出版商
Public Library of Science
简介
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 …
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G Matullo, S Guarrera, M Betti, G Fiorito, D Ferrante… - PloS one, 2013