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.
| Original language | English |
|---|---|
| Pages (from-to) | 1129-1135 |
| Number of pages | 7 |
| Journal | Carcinogenesis |
| Volume | 36 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Aug 16 2015 |
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ASJC Scopus subject areas
- Cancer Research
- Medicine(all)
Cite this
Gene-asbestos interaction in malignant pleural mesothelioma susceptibility. / 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.
In: Carcinogenesis, Vol. 36, No. 10, 16.08.2015, p. 1129-1135.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Gene-asbestos interaction in malignant pleural mesothelioma susceptibility
AU - Tunesi, Sara
AU - Ferrante, Daniela
AU - Mirabelli, Dario
AU - Andorno, Silvano
AU - Betti, Marta
AU - Fiorito, Giovanni
AU - Guarrera, Simonetta
AU - Casalone, Elisabetta
AU - Neri, Monica
AU - Ugolini, Donatella
AU - Bonassi, Stefano
AU - Matullo, Giuseppe
AU - Dianzani, Irma
AU - Magnani, Corrado
PY - 2015/8/16
Y1 - 2015/8/16
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84943745697&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84943745697&partnerID=8YFLogxK
U2 - 10.1093/carcin/bgv097
DO - 10.1093/carcin/bgv097
M3 - Article
C2 - 26139392
AN - SCOPUS:84943745697
VL - 36
SP - 1129
EP - 1135
JO - Carcinogenesis
JF - Carcinogenesis
SN - 0143-3334
IS - 10
ER -