Oxidative stress in susceptibility to breast cancer: study in Spanish population

BMC Cancer

Patricia Rodrigues⁷  Griselda de Marco⁵  Jessica Furriol⁶  Maria Luisa Mansego⁴  Mónica Pineda-Alonso³  Anna Gonzalez-Neira²  Juan Carlos Martin-Escudero³  Javier Benitez²  Ana Lluch¹  Felipe J Chaves⁵  Pilar Eroles⁷ 

[1] Department of Haematology and Medical Oncology, Hospital Clínico Universitario de Valencia, Valencia, Spain

[2] Genotyping Unit, CEGEN, Spanish National Cancer Center (CNIO), Madrid, Spain

[3] Internal Medicine, Hospital Rio Hortega, University of Valladolid, Valladolid, Spain

[4] Current address: Department of Nutrition and Food Sciences, Physiology and Toxicology, University of Navarra, Pamplona, Spain

[5] Genotyping and Genetic Diagnosis Unit, Hospital Clínico Universitario de Valencia INCLIVA Biomedical Research Institute, Valencia, Spain

[6] Current address: Clinical Institute 1 CCBIO, University of Bergen, Bergen, Norway

[7] INCLIVA Biomedical Research Institute, Valencia, Spain

关键词: Multifactor dimensionality reduction;    Gene-gene interactions;    Single nucleotide polymorphisms;    Oxidative stress;    Breast cancer;   

Others  :  1118037
DOI  :  10.1186/1471-2407-14-861

 received in 2014-03-13, accepted in 2014-11-14,  发布年份 2014

【 摘 要 】

Background

Alterations 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.

Methods

We 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.

Results

Six 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]).

Conclusions

The 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.

【 授权许可】

   
2014 Rodrigues et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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