Abstract
BackgroundAlterations in the redox balance are involved in the origin, promotion and progression of cancer. Inter-individual differences in the oxidative stress regulation can explain a part of the variability in cancer susceptibility.The aim of this study was to evaluate if polymorphisms in genes codifying for the different systems involved in oxidative stress levels can have a role in susceptibility to breast cancer.MethodsWe have analyzed 76 single base polymorphisms located in 27 genes involved in oxidative stress regulation by SNPlex technology. First, we have tested all the selected SNPs in 493 breast cancer patients and 683 controls and we have replicated the significant results in a second independent set of samples (430 patients and 803 controls). Gene-gene interactions were performed by the multifactor dimensionality reduction approach.ResultsSix polymorphisms rs1052133 (OGG1), rs406113 and rs974334 (GPX6), rs2284659 (SOD3), rs4135225 (TXN) and rs207454 (XDH) were significant in the global analysis. The gene-gene interactions demonstrated a significant four-variant interaction among rs406113 (GPX6), rs974334 (GPX6), rs105213 (OGG1) and rs2284659 (SOD3) (p-value = 0.0008) with high-risk genotype combination showing increased risk for breast cancer (OR = 1.75 [95% CI; 1.26-2.44]).ConclusionsThe results of this study indicate that different genotypes in genes of the oxidant/antioxidant pathway could affect the susceptibility to breast cancer. Furthermore, our study highlighted the importance of the analysis of the epistatic interactions to define with more accuracy the influence of genetic variants in susceptibility to breast cancer.
Highlights
Alterations in the redox balance are involved in the origin, promotion and progression of cancer
Thereupon, we chose the polymorphisms that showed marginally significant association (p-value < = 0.15), and we replicated the procedure in a second independent group (n = 1233) where we included 430 female patients diagnosed for breast cancer (BC) between the years 1988–1998 at the Clinic Hospital of Valencia (Spain) and 803 samples from cancer-free women recruited at the blood donor bank at the same Hospital
Our results suggest that different genotypes in genes of the oxidant/antioxidant pathway could affect the susceptibility to breast cancer
Summary
Alterations in the redox balance are involved in the origin, promotion and progression of cancer. Another study showed that mice lacking the antioxidant enzyme Prdx had a shortened lifespan owing to the development, beginning at about 9 months, of severe hemolytic anemia and several malignant cancers [13]. In this context, single nucleotide polymorphisms (SNPs) in components of the cellular redox systems can modify the redox balance and take part in both the BC initiation and/or progression, as well as determine possible therapeutic treatments [14,15,16,17]
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