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

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 5 1.69, 95% CI 5 1.04-2.74; p 5 0.034), and in those with the Ala/Ala genotypes at codon 16 within MnSOD (OR 5 3.07, 95% CI 5 1.55-6.05; p 5 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.

The role of GSTA2 polymorphisms and haplotypes in breast cancer susceptibility: A case-control study in the Portuguese population

“…MAF values obtained were in accordance with the ones reported in the HapMap project (http://www.hapmap.org/). The data available in the literature in Caucasian populations, the genotype frequencies for the GSTA2 S112T polymorphism and the values reported in these studies are ambiguous, two of them are in agreement with the data obtained in this study (16,29), while further two studies report different frequencies (17,30). The SNP frequencies in control and cancer population are not significantly different and the crude and adjusted ORs associated with each polymorphism are not significantly different (Table III), suggesting that these polymorphisms are not associated with breast cancer susceptibility.…”

XRCC1 and ERCC1 variants modify malignant mesothelioma risk: A case–control study

“…Some of the studied DNA repair genes revealed significant associations, but most of them disappeared after Bonferroni correction for multiple analyses. A further study from the same group reported an association with SOD2 16A [34].…”

“…Since several of the SNPs that were studied in this work were the object of two previous papers [33,34], we also carried out a meta-analysis. Gemignani et al [33] used two panels of controls: panel 1 included individuals whose asbestos exposure was known, whereas panel 2 included blood donors whose asbestos exposure had not been evaluated.…”

“…Meta-analysis was performed for those SNPs that were studied either by Gemignani et al [33] or Landi et al [34] and in this study. We evaluated also the heterogeneity between these studies and we found that our study and Gemignani et al were homogeneous, whereas our study and Landi et al were heterogeneous.…”

CREST biorepository for translational studies on malignant mesothelioma, lung cancer and other respiratory tract diseases: Informatics infrastructure and standardized annotation

“…The endpoints measured in these studies included: levels of circulating proteins (HER-2/neu, mesothelin, osteopontin, mutated K-ras), growth factors (PDGF-AB, HGF, EGF, SCF) or antibodies (anti-p53), erythrocyte glycophorin-A variants, DNA adducts, micronuclei, DNA repair activities, SV40, single-nucleotide polymorphisms in metabolic, DNA repair or other genes, and microRNA. A list of published studies has been previously reported (7), while most recent publications have been added to the references (19)(20)(21)(22)(23)(24)(25)(26).…”