Gene–asbestos interaction in malignant pleural mesothelioma susceptibility

Sara Tunesi, Daniela Ferrante, Dario Mirabelli, Silvano Andorno, Marta Betti, Giovanni Fiorito, Simonetta Guarrera, Elisabetta Casalone, Monica Neri, Donatella Ugolini, Stefano Bonassi, Giuseppe Matullo (+2 others)
2015 Carcinogenesis  
These authors contributed equally to this work. 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
more » ... ms (SNPs) previously identified through a genome-wide association study on Italian subjects. In the present study, we assessed geneasbestos 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.
doi:10.1093/carcin/bgv097 pmid:26139392 fatcat:c2hk6yopcrhlxc5rv62y7nqwwq