title: 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.affiliation: Department of Translational Medicine, Unit of Medical Statistics and Cancer Epidemiology, CPO Piemonte and University of Piemonte Orientale, Novara, Italy, Center for Cancer Epidemiology and Prevention, City of Health and Science Hospital, Turin, Italy, sara.tunesi@med.uniupo.it.
authors.forename: Sara
authors.initials: S
authors.lastname: Tunesi
authors.affiliation: Department of Translational Medicine, Unit of Medical Statistics and Cancer Epidemiology, CPO Piemonte and University of Piemonte Orientale, Novara, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ferrante
authors.affiliation: Center for Cancer Epidemiology and Prevention, City of Health and Science Hospital, Turin, Italy, Interdepartmental Center "G. Scansetti", University of Turin, Turin, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Mirabelli
authors.affiliation: Department of Translational Medicine, Unit of Medical Statistics and Cancer Epidemiology, CPO Piemonte and University of Piemonte Orientale, Novara, Italy.
authors.forename: Silvano
authors.initials: S
authors.lastname: Andorno
authors.affiliation: Department of Health Sciences, University of Piemonte Orientale, Novara, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Betti
authors.affiliation: Genomic Variation in Human Population and Complex Diseases Unit, Human Genetics Foundation, Turin, Italy, Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Fiorito
authors.affiliation: Genomic Variation in Human Population and Complex Diseases Unit, Human Genetics Foundation, Turin, Italy, Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Guarrera
authors.affiliation: Genomic Variation in Human Population and Complex Diseases Unit, Human Genetics Foundation, Turin, Italy, Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Casalone
authors.affiliation: Unit of Clinical and Molecular Epidemiology, IRCCS San Raffaele Pisana, Rome, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Neri
authors.affiliation: Department of Internal Medicine, University of Genoa and IRCSS AOU San Martino-IST-Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Ugolini
authors.affiliation: Unit of Clinical and Molecular Epidemiology, IRCCS San Raffaele Pisana, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonassi
authors.affiliation: Genomic Variation in Human Population and Complex Diseases Unit, Human Genetics Foundation, Turin, Italy, Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Matullo
authors.affiliation: Department of Health Sciences, University of Piemonte Orientale, Novara, Italy.
authors.forename: Irma
authors.initials: I
authors.lastname: Dianzani
authors.affiliation: Department of Translational Medicine, Unit of Medical Statistics and Cancer Epidemiology, CPO Piemonte and University of Piemonte Orientale, Novara, Italy, Interdepartmental Center "G. Scansetti", University of Turin, Turin, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Magnani
mesh_terms: D000328:Adult; D000368:Aged; D001194:Asbestos / Q000633:toxicity*; D005260:Female; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D008297:Male; D008654:Mesothelioma / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D016273:Occupational Exposure; D010997:Pleural Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D001194:Asbestos