Metabolic genotypes as modulators of asbestos-related pleural malignant mesothelioma risk: A comparison of Finnish and Italian populations

International Journal of Hygiene and Environmental Health . 2006 May 10; [Epub ahead of print] [Link]

Monica Neri^a, Emanuela Taioli^b, Rosangela Filiberti^c, Giovanni Paolo Ivaldi^d, Pier Aldo Canessa^e, Anna Verna^f, Paola Marroni^g, Riccardo Puntoni^a, Ari Hirvonen^h and Seymour Garte^{b, i}

^aEpidemiology and Biostatistics, National Cancer Research Institute, largo Rosanna Benzi 10, 16132 Genoa, Italy
^bUniversity of Pittsburgh Cancer Institute and Graduate School of Public Health, Pittsburgh, USA
^cMolecular Epidemiology, National Cancer Research Institute, Genoa, Italy
^dPneumology, AO Villa Scassi, Genoa, Italy
^ePneumology, Ospedale S. Bartolomeo, Sarzana, Italy
^fSurgical Oncology B, National Cancer Research Institute, Genoa, Italy
^gClinical Pathology, National Cancer Research Institute, Genoa, Italy
^hIndustrial Hygiene and Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland
ⁱGenetics Research Institute ONLUS, Milan, Italy

Received 14 October 2005;  revised 30 January 2006;  accepted 30 March 2006.  Available online 11 May 2006.

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.

Keywords: Asbestos; EPHX1; GSTM1; GSTT1; NAT2; Malignant mesothelioma

Abbreviations: MM, pleural malignant mesothelioma; NAT2, N-acetyltransferase 2; EPHX1, microsomal epoxide hydrolase, GSTM1 and GSTT1, glutathione S-transferase M1 and T1; CYP1A1, cytochrome P450 1A1