Association between SNPs in defined functional pathways and risk of early or late toxicity as well as individual radiosensitivity

Strahlenther Onkol. 2015 Jan;191(1):59-66. doi: 10.1007/s00066-014-0741-y. Epub 2014 Aug 26.


Background and purpose: The aim of this study was to determine the impact of functional single nucleotide polymorphism (SNP) pathways involved in the ROS pathway, DNA repair, or TGFB1 signaling on acute or late normal toxicity as well as individual radiosensitivity.

Materials and methods: Patients receiving breast-conserving surgery and radiotherapy were examined either for erythema (n = 83), fibrosis (n = 123), or individual radiosensitivity (n = 123). The 17 SNPs analyzed are involved in the ROS pathway (GSTP1, SOD2, NQO1, NOS3, XDH), DNA repair (XRCC1, XRCC3, XRCC6, ERCC2, LIG4, ATM) or TGFB signaling (SKIL, EP300, APC, AXIN1, TGFB1). Associations with biological and clinical endpoints were studied for single SNPs but especially for combinations of SNPs assuming that a SNP is either beneficial or deleterious and needs to be weighted.

Results: With one exception, no significant association was seen between a single SNP and the three endpoints studied. No significant associations were also observed when applying a multi-SNP model assuming that each SNP was deleterious. In contrast, significant associations were obtained when SNPs were suggested to be either beneficial or deleterious. These associations increased, when each SNP was weighted individually. Detailed analysis revealed that both erythema and individual radiosensitivity especially depend on SNPs affecting DNA repair and TGFB1 signaling, while SNPs in ROS pathway were of minor importance.

Conclusion: Functional pathways of SNPs may be used to form a risk score allowing to predict acute and late radiation-induced toxicity but also to unravel the underlying biological mechanisms.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / radiotherapy*
  • DNA Repair / genetics*
  • Female
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics
  • Germany / epidemiology
  • Humans
  • Incidence
  • Linkage Disequilibrium / genetics
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Models, Genetic
  • Polymorphism, Single Nucleotide / genetics*
  • Radiation Injuries / epidemiology
  • Radiation Injuries / genetics*
  • Radiation Tolerance / genetics*
  • Retrospective Studies
  • Risk Assessment / methods
  • Signal Transduction / genetics
  • Transforming Growth Factor beta1 / genetics


  • Biomarkers, Tumor
  • Genetic Markers
  • TGFB1 protein, human
  • Transforming Growth Factor beta1