TY - JOUR
T1 - XRCC1 and ERCC1 variants modify malignant mesothelioma risk
T2 - A case-control study
AU - Betti, M.
AU - Ferrante, D.
AU - Padoan, M.
AU - Guarrera, S.
AU - Giordano, M.
AU - Aspesi, A.
AU - Mirabelli, D.
AU - Casadio, C.
AU - Ardissone, F.
AU - Ruffini, E.
AU - Betta, P. G.
AU - Libener, R.
AU - Guaschino, R.
AU - Matullo, G.
AU - Piccolini, E.
AU - Magnani, C.
AU - Dianzani, I.
N1 - Funding Information:
This study was made possible by grants from Regione Piemonte Ricerca Sanitaria Finalizzata 2007, 2008, 2009, CIPE, Fondazione Buzzi Unicem Onlus 2007, AIRC 2007–2010.
Funding Information:
We are greatly indebted to all those who agreed to partecipate in this study and contributed to it, in particular the MPM patients, their physicians, the controls and their family doctors. We are also indebted to the heads and the medical staff of the Units of Oncology (M. Botta, B. Castagneto, A. Muzio and D. Degiovanni) and Medicine (V. Cocito) of Casale Monferrato Hospital. This study was made possible by grants from Regione Piemonte Ricerca Sanitaria Finalizzata 2007, 2008, 2009, CIPE, Fondazione Buzzi Unicem Onlus 2007, AIRC 2007–2010.
PY - 2011/3/15
Y1 - 2011/3/15
N2 - Malignant pleural mesothelioma (MPM) is a rare aggressive tumor associated with asbestos exposure. The possible role of genetic factors has also been suggested and MPM has been associated with single nucleotide polymorphisms (SNPs) of xenobiotic and oxidative metabolism enzymes. We have identified an association of the DNA repair gene XRCC1 with MPM in the population of Casale Monferrato, a town exposed to high asbestos pollution. To extend this observation we examined 35 SNPs in 15 genes that could be involved in MPM carcinogenicity in 220 MPM patients and 296 controls from two case-control studies conducted in Casale (151 patients, 252 controls) and Turin (69 patients, 44 controls), respectively. Unconditional multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Two DNA repair genes were associated with MPM, i.e. XRCC1 and ERCC1. Considering asbestos-exposed only, the risk increased with the increasing number of XRCC1-399Q alleles (Casale: OR. =1.44, 95%CI 1.02-2.03; Casale + Turin: OR. =1.34, 95%CI 0.98-1.84) or XRCC1 -77T alleles (Casale + Turin: OR. =1.33, 95%CI 0.97-1.81). The XRCC1-TGGGGGAACAGA haplotype was significantly associated with MPM (Casale: OR. =1.76, 95%CI 1.04-2.96). Patients heterozygotes for ERCC1 N118N showed an increased OR in all subjects (OR. =1.66, 95%CI 1.06-2.60) and in asbestos-exposed only (OR. =1.59, 95%CI 1.01-2.50). When the dominant model was considered (i.e. ERCC1 heterozygotes CT plus homozygotes CC versus homozygotes TT) the risk was statistically significant both in all subjects (OR. =1.61, 95%CI 1.06-2.47) and in asbestos-exposed only (OR. =1.56, 95%CI 1.02-2.40). The combination of ERCC1 N118N and XRCC1 R399Q was statistically significant (Casale: OR. =2.02, 95%CI 1.01-4.05; Casale + Turin: OR. =2.39, 95%CI 1.29-4.43). The association of MPM with DNA repair genes support the hypothesis that an increased susceptibility to DNA damage may favour asbestos carcinogenicity.
AB - Malignant pleural mesothelioma (MPM) is a rare aggressive tumor associated with asbestos exposure. The possible role of genetic factors has also been suggested and MPM has been associated with single nucleotide polymorphisms (SNPs) of xenobiotic and oxidative metabolism enzymes. We have identified an association of the DNA repair gene XRCC1 with MPM in the population of Casale Monferrato, a town exposed to high asbestos pollution. To extend this observation we examined 35 SNPs in 15 genes that could be involved in MPM carcinogenicity in 220 MPM patients and 296 controls from two case-control studies conducted in Casale (151 patients, 252 controls) and Turin (69 patients, 44 controls), respectively. Unconditional multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Two DNA repair genes were associated with MPM, i.e. XRCC1 and ERCC1. Considering asbestos-exposed only, the risk increased with the increasing number of XRCC1-399Q alleles (Casale: OR. =1.44, 95%CI 1.02-2.03; Casale + Turin: OR. =1.34, 95%CI 0.98-1.84) or XRCC1 -77T alleles (Casale + Turin: OR. =1.33, 95%CI 0.97-1.81). The XRCC1-TGGGGGAACAGA haplotype was significantly associated with MPM (Casale: OR. =1.76, 95%CI 1.04-2.96). Patients heterozygotes for ERCC1 N118N showed an increased OR in all subjects (OR. =1.66, 95%CI 1.06-2.60) and in asbestos-exposed only (OR. =1.59, 95%CI 1.01-2.50). When the dominant model was considered (i.e. ERCC1 heterozygotes CT plus homozygotes CC versus homozygotes TT) the risk was statistically significant both in all subjects (OR. =1.61, 95%CI 1.06-2.47) and in asbestos-exposed only (OR. =1.56, 95%CI 1.02-2.40). The combination of ERCC1 N118N and XRCC1 R399Q was statistically significant (Casale: OR. =2.02, 95%CI 1.01-4.05; Casale + Turin: OR. =2.39, 95%CI 1.29-4.43). The association of MPM with DNA repair genes support the hypothesis that an increased susceptibility to DNA damage may favour asbestos carcinogenicity.
KW - Asbestos
KW - DNA repair genes
KW - Haplotype
KW - Mesothelioma
KW - Single nucleotide polymorphisms (SNPs)
UR - https://www.scopus.com/pages/publications/79952453654
U2 - 10.1016/j.mrfmmm.2011.01.001
DO - 10.1016/j.mrfmmm.2011.01.001
M3 - Article
SN - 0027-5107
VL - 708
SP - 11
EP - 20
JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
IS - 1-2
ER -
SDG 11 Sustainable Cities and Communities