Pleural malignant mesothelioma, genetic susceptibility and asbestos exposure

Monica Neri, Rosangela Filiberti, Emanuela Taioli, Seymour Garte, Valentina Paracchini, Claudia Bolognesi, Pier Aldo Canessa, Vincenzo Fontana, Giovanni Paolo Ivaldi, Anna Verna, Stefano Bonassi, Riccardo Puntoni

Research output: Contribution to journalArticle

Abstract

Pleural malignant mesothelioma (MM) is a rare but extremely aggressive cancer. The limited impact of standard therapeutic treatments on survival rates makes the identification of factors that increase the individual risk a leading priority. The high proportion of cases explained by exposure to asbestos has guided intervention policies to an effective ban of this compound from our environment. However, MM cannot be solely attributed to this agent, and the role of predisposing factors and their interaction with asbestos exposure is increasingly studied. The role of mEH, GSTM1, GSTT1, NAT2, and CYP1A1 genotypes in modulating susceptibility to MM was examined in a case-control study of 80 subjects with a confirmed diagnosis of MM and 255 controls. Subjects with low mEH activity showed a significantly increased risk of MM (OR, 2.51; 95% CI, 1.11-5.68). The association was stronger in the group with low asbestos exposure (OR, 7.83; 95% CI, 0.98-62.60). A significant increased risk of MM was also found in NAT2 fast acetylators (OR, 1.74; 95% CI, 1.02-2.96). The presence of synergisms between genotypes, i.e., mEH and NAT2 (LRT for heterogeneity p <0.023), mEH and GSTM1 (LRT p <0.061), and NAT2 and GSTM1 (LRT p <0.049), combined with the interaction observed with exposure to asbestos, suggests the presence of gene-environment and gene-gene interactions in the development of MM, although the size of the study group does not allow to draw clearcut conclusions. Since genetic polymorphisms can also modify the extent of genetic damage occurring in subjects exposed to carcinogens, we measured the frequency of micronuclei in peripheral blood lymphocytes of a subgroup of MM cases. The limited number of cases (28) did not allow to observe significant effects. In conclusion, these results strengthen the hypothesis that individual susceptibility to MM can be modulated by the interaction between polymorphic genes involved in the metabolism and the intensity of asbestos exposure.

Original languageEnglish
Pages (from-to)36-44
Number of pages9
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume592
Issue number1-2
DOIs
Publication statusPublished - Dec 30 2005

Keywords

  • Asbestos
  • CYP1A1
  • Gene-environment interaction
  • GSTM1
  • GSTT1
  • Malignant mesothelioma
  • mEH
  • NAT2

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Molecular Biology

Fingerprint Dive into the research topics of 'Pleural malignant mesothelioma, genetic susceptibility and asbestos exposure'. Together they form a unique fingerprint.

  • Cite this