Polymorphisms of glutathione-S-transferase M1 and manganese superoxide dismutase are associated with the risk of malignant pleural mesothelioma

Stefano Landi, Federica Gemignani, Monica Neri, Roberto Barale, Stefano Bonassi, Fabio Bottari, Pier Aldo Canessa, Federico Canzian, Marcello Ceppi, Rosangela Filiberti, Gian Paolo Ivaldi, Manlio Mencoboni, Paola Scaruffi, Gian Paolo Tonini, Luciano Mutti, Riccardo Puntoni

Research output: Contribution to journalArticle

Abstract

Individual response to oxidative stress, due to exposure to asbestos fibres plays a significant role in the malignant pleural mesothelioma (MPM) etiology. The differential impact on MPM risk of polymorphic alleles of glutathione-S-transferases (GSTs) and manganese superoxide dismutase (MnSOD/SOD2) genes involved in the defence against oxidative damage has been investigated. Ninety cases of MPM and 395 controls were genotyped using the arrayed-primer extension technique. Logistic regression analysis was applied to assess the predictive role of single nucleotide polymorphisms (SNPs) potentially involved in MPM carcinogenesis after adjustment for potential confounders. An increased risk of MPM was found in subjects bearing a GSTM1 null allele (OR = 1.69, 95% CI = 1.04-2.74; p = 0.034), and in those with the Ala/Ala genotypes at codon 16 within MnSOD (OR = 3.07, 95% CI = 1.55-6.05; p = 0.001). A stronger effect of MnSOD was observed among patients without a clear exposure to asbestos fibres. No effect was found for GSTA2, GSTA4, GSTM3, GSTP1 and GSTT1 genes. These findings, if replicated, contribute substantial evidence to the hypothesis that oxidative stress and cellular antireactive oxygen species systems are involved in the pathogenesis and in the natural history of MPM.

Original languageEnglish
Pages (from-to)2739-2743
Number of pages5
JournalInternational Journal of Cancer
Volume120
Issue number12
DOIs
Publication statusPublished - Jun 15 2007

Keywords

  • Genetic glutathione transferase
  • Mesothelioma
  • Molecular epidemiology
  • Oxidative stress
  • Polymorphism
  • Superoxide dismutase

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Landi, S., Gemignani, F., Neri, M., Barale, R., Bonassi, S., Bottari, F., Canessa, P. A., Canzian, F., Ceppi, M., Filiberti, R., Ivaldi, G. P., Mencoboni, M., Scaruffi, P., Tonini, G. P., Mutti, L., & Puntoni, R. (2007). Polymorphisms of glutathione-S-transferase M1 and manganese superoxide dismutase are associated with the risk of malignant pleural mesothelioma. International Journal of Cancer, 120(12), 2739-2743. https://doi.org/10.1002/ijc.22590