title: Metabolic genotypes as modulators of asbestos-related pleural malignant mesothelioma risk: a comparison of Finnish and Italian populations.
abstract: The role of CYP1A1, GSTM1, GSTT1, EPHX1, and NAT2 genotypes in susceptibility to malignant mesothelioma (MM) was compared in two case-control studies, previously conducted in two countries where different types of asbestos fibers have been used [Hirvonen et al., 1995. Inherited GSTM1 and NAT2 defects as concurrent risk modifiers in asbestos-related human malignant mesothelioma. Cancer Res. 55, 2981-2983; Hirvonen et al., 1996. Glutathione S-Transferase and N-Acetyltransferase genotypes and asbestos-associated pulmonary disorders. J. Natl. Cancer Inst.88, 1853-1856; Neri et al., 2005. Pleural malignant mesothelioma, genetic susceptibility and asbestos exposure. Mutat. Res. 592, 36-44]. Fifty-seven asbestos-exposed MM patients and 255 controls were recruited in Italy, 48 cases and 121 controls in Finland. In order to make the two studies comparable, they have been updated and new genotyping analyses have been performed. The NAT2 fast acetylator and EPHX1 low-activity genotypes were positively associated with MM in the Italian study, while they were negatively associated with this malignancy in the Finnish one. A combined significant effect was also observed in the Italian study for the NAT2 fast acetylator and EPHX1 low-activity genotypes, while this combination was protective in the Finnish study. Combination of NAT2 fast acetylator and GSTM1 null genotype posed a significantly increased risk of MM in the Italian, but not in the Finnish study. The opposite results obtained in Finland and Italy may be ascribed to random chance, but a role may be hypothesized for the fact that different types of asbestos have been used in the two countries.
authors.affiliation: Epidemiology and Biostatistics, National Cancer Research Institute, largo Rosanna Benzi 10, 16132 Genoa, Italy. monica.neri@istge.it
authors.forename: Monica
authors.initials: M
authors.lastname: Neri
authors.forename: Emanuela
authors.initials: E
authors.lastname: Taioli
authors.forename: Rosangela
authors.initials: R
authors.lastname: Filiberti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Paolo Ivaldi
authors.forename: Pier
authors.initials: P
authors.lastname: Aldo Canessa
authors.forename: Anna
authors.initials: A
authors.lastname: Verna
authors.forename: Paola
authors.initials: P
authors.lastname: Marroni
authors.forename: Riccardo
authors.initials: R
authors.lastname: Puntoni
authors.forename: Ari
authors.initials: A
authors.lastname: Hirvonen
authors.forename: Seymour
authors.initials: S
authors.lastname: Garte
mesh_terms: D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D001194:Asbestos / Q000633:toxicity*; D016022:Case-Control Studies; D004851:Epoxide Hydrolases / Q000235:genetics; D005387:Finland; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007558:Italy; D008654:Mesothelioma / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics*; D016273:Occupational Exposure / Q000009:adverse effects; D016017:Odds Ratio; D010997:Pleural Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics*
chemical_list: D001191:Arylamine N-Acetyltransferase; D001194:Asbestos; D004851:Epoxide Hydrolases; D005982:Glutathione Transferase; C478900:NAT2 protein, human