The influence of polymorphisms in genes related to oxidative stress on breast cancer survival in a German case-control study

Background: In Germany, about 17,500 women die from breast cancer annually. As radio- and chemotherapy partly exert their cytotoxic effects by increased formation of reactive oxygen species, variants in oxidative stress-related genes might influence efficacy of treatment and therefore modify survival time. The aim of this study was thus to evaluate the effect of 109 common single nucleotide polymorphisms (SNPs) in 22 oxidative stress-related genes on all-cause mortality in breast cancer patients. Methods: Incident breast cancer patients aged 50–74 and diagnosed between 2002–2005 from the German population-based case-control study MARIE were followed up through population registries until the end of 2009 (MARIEplus). For this analysis, 1,072 patients from the Rhein-Neckar-Heidelberg region with genotype data were included. A log-additive mode of inheritance for the SNPs was assumed. Cox proportional hazards models were employed to calculate hazard ratios (HR) and 95% confidence intervals (CI, stratified by age at diagnosis, with adjustment for potential prognostic factors (tumor stage, receptor status, diabetes, previous cancer(s), current hormone replacement therapy, radio-/chemotherapy, smoking status). Results: Median follow-up time was 5.8 years. 161 out of 1,072 patients died. SNPs associated with increased hazard of death were found in the transcription factor NFE2L2 (per allele: rs10183914, HR 1.3 (CI 1.1–1.7), rs1806649, HR 1.3 (CI 1.0–1.7)) as well as in H2O2- or glutathione-related genes such as peroxiredoxin-6 and thioredoxin, while SNPs in heme oxygenase and thioredoxin reductase-2 were associated with decreased risk of death. Further analyses will address breast cancer-specific survival, effect heterogeneity by therapy as well as adjustment for multiple testing. Conclusions: Our results suggest that some oxidative stress-related genes may affect overall survival in breast cancer patients, but confirmation in independent data sets is warranted.