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01-01-2015 | Original article

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

Authors: Sebastian Reuther, PhD, Silke Szymczak, PhD, Annette Raabe, PhD, Kerstin Borgmann, PhD, Andreas Ziegler, PhD, Cordula Petersen, MD, Prof Dr. Ekkehard Dikomey, PhD, Ulrike Hoeller, MD

Published in: Strahlentherapie und Onkologie | Issue 1/2015

Abstract

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.

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Title: Association between SNPs in defined functional pathways and risk of early or late toxicity as well as individual radiosensitivity
Authors: Sebastian Reuther, PhD
Silke Szymczak, PhD
Annette Raabe, PhD
Kerstin Borgmann, PhD
Andreas Ziegler, PhD
Cordula Petersen, MD
Prof Dr. Ekkehard Dikomey, PhD
Ulrike Hoeller, MD
Publication date: 01-01-2015
Publisher: Springer Berlin Heidelberg
Published in: Strahlentherapie und Onkologie / Issue 1/2015
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI: https://doi.org/10.1007/s00066-014-0741-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Background and purpose

Materials and methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background and purpose

Materials and methods

Results

Conclusion

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