Gene-asbestos interaction in malignant pleural mesothelioma susceptibility

Carcinogenesis 2015 July 2 [Epub ahead of print] [Link]

Tunesi S, Ferrante D, Mirabelli D, Andorno S, Betti M, Fiorito G, Guarrera S, Casalone E, Neri M, Ugolini D, Bonassi S, Matullo G, Dianzani I, Magnani C.


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 fifteen 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 (RERI) and Synergy Index (SI) 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.