Polymorphisms of glutathione-S-transferase M1 and manganese superoxide dismutase are associated with the risk of malignant pleural mesothelioma.
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.
Landi
Stefano
S
Department of Biology, University of Pisa, Pisa, Italy.
Gemignani
Federica
F
Neri
Monica
M
Barale
Roberto
R
Bonassi
Stefano
S
Bottari
Fabio
F
Canessa
Pier Aldo
PA
Canzian
Federico
F
Ceppi
Marcello
M
Filiberti
Rosangela
R
Ivaldi
Gian Paolo
GP
Mencoboni
Manlio
M
Scaruffi
Paola
P
Tonini
Gian Paolo
GP
Mutti
Luciano
L
Puntoni
Riccardo
R
D000368:Aged; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008654:Mesothelioma / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D008875:Middle Aged; D016017:Odds Ratio; D010997:Pleural Neoplasms / Q000235:genetics / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013482:Superoxide Dismutase / Q000235:genetics*
D005982:Glutathione Transferase; D013482:Superoxide Dismutase