Gene-asbestos interaction in malignant pleural mesothelioma susceptibility.

Abstract

Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, on average less than 10% of subjects highly exposed to asbestos develop MPM, suggesting the possible involvement of other risk factors. To identify the genetic factors that may modulate the risk of MPM, we conducted a gene-environment interaction analysis including asbestos exposure and 15 single nucleotide polymorphisms (SNPs) previously identified through a genome-wide association study on Italian subjects. In the present study, we assessed gene-asbestos interaction on MPM risk using relative excess risk due to interaction and synergy index for additive interaction and V index for multiplicative interaction. Generalized multifactor dimensionality reduction (GMDR) analyses were also performed. Positive deviation from additivity was found for six SNPs (rs1508805, rs2501618, rs4701085, rs4290865, rs10519201, rs763271), and four of them (rs1508805, rs2501618, rs4701085, rs10519201) deviated also from multiplicative models. However, after Bonferroni correction, deviation from multiplicative model was still significant for rs1508805 and rs4701085 only. GMDR analysis showed a strong MPM risk due to asbestos exposure and suggested a possible synergistic effect between asbestos exposure and rs1508805, rs2501618 and rs5756444. Our results suggested that gene-asbestos interaction may play an additional role on MPM susceptibility, given that asbestos exposure appears as the main risk factor.

• Authors: Sara Tunesi, Daniela Ferrante, Dario Mirabelli, Silvano Andorno, Marta Betti, Giovanni Fiorito, Simonetta Guarrera, Elisabetta Casalone, Monica Neri, Donatella Ugolini, Stefano Bonassi, Giuseppe Matullo, Irma Dianzani, Corrado Magnani
• Journal: Carcinogenesis (Carcinogenesis) Vol. 36 Issue 10 Pg. 1129-35 (Oct 2015) ISSN: 1460-2180 [Electronic] England
• PMID: 26139392 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Asbestos

Topics

• Adult
• Aged
• Asbestos (toxicity)
• Female
• Gene-Environment Interaction
• Genetic Association Studies
• Humans
• Lung Neoplasms (chemically induced, genetics, pathology)
• Male
• Mesothelioma (chemically induced, genetics, pathology)
• Mesothelioma, Malignant
• Middle Aged
• Occupational Exposure
• Pleural Neoplasms (chemically induced, genetics, pathology)
• Polymorphism, Single Nucleotide
• Risk Factors