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Polymorphisms of glutathione‐ S ‐transferase M1 and manganese superoxide dismutase are associated with the risk of malignant pleural mesothelioma
Author(s) -
Landi Stefano,
Gemignani Federica,
Neri Monica,
Barale Roberto,
Bonassi Stefano,
Bottari Fabio,
Canessa Pier Aldo,
Canzian Federico,
Ceppi Marcello,
Filiberti Rosangela,
Ivaldi Gian Paolo,
Mencoboni Manlio,
Scaruffi Paola,
Tonini Gian Paolo,
Mutti Luciano,
Puntoni Riccardo
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22590
Subject(s) - gstp1 , mesothelioma , sod2 , oxidative stress , superoxide dismutase , single nucleotide polymorphism , biology , genotype , allele , carcinogenesis , glutathione s transferase , medicine , pathology , glutathione , immunology , gastroenterology , cancer research , genetics , cancer , gene , endocrinology , biochemistry , enzyme
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. © 2007 Wiley‐Liss, Inc.