Gene-asbestos interaction in malignant pleural mesothelioma susceptibility

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...

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Bibliographic Details
Published in:Carcinogenesis (New York) 2015-10, Vol.36 (10), p.1129-1135
Main Authors: Tunesi, Sara, Ferrante, Daniela, Mirabelli, Dario, Andorno, Silvano, Betti, Marta, Fiorito, Giovanni, Guarrera, Simonetta, Casalone, Elisabetta, Neri, Monica, Ugolini, Donatella, Bonassi, Stefano, Matullo, Giuseppe, Dianzani, Irma, Magnani, Corrado
Format: Article
Language:English
Subjects:
Adult
Aged
Asbestos - toxicity
Female
Gene-Environment Interaction
Genetic Association Studies
Humans
Lung Neoplasms - chemically induced
Lung Neoplasms - genetics
Lung Neoplasms - pathology
Male
Mesothelioma - chemically induced
Mesothelioma - genetics
Mesothelioma - pathology
Mesothelioma, Malignant
Middle Aged
Occupational Exposure
Pleural Neoplasms - chemically induced
Pleural Neoplasms - genetics
Pleural Neoplasms - pathology
Polymorphism, Single Nucleotide
Risk Factors
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Summary: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.
ISSN:0143-3334
1460-2180
DOI:10.1093/carcin/bgv097