XRCC1 Polymorphism Associated With Late Toxicity After Radiation Therapy in Breast Cancer Patients

Research output: Contribution to journalArticle

  • External authors:
  • Petra Seibold
  • Sabine Behrens
  • Peter Schmezer
  • Irmgard Helmbold
  • Gillian Barnett
  • Charlotte Coles
  • John Yarnold
  • Christopher J Talbot
  • Takashi Imai
  • David Azria
  • C Anne Koch
  • Alison M Dunning
  • Judith M Bliss
  • R Paul Symonds
  • Tim Rattay
  • Tomo Suga
  • Sarah L Kerns
  • Celine Bourgier
  • Katherine A Vallis
  • Marie-Luise Sautter-Bihl
  • Johannes Claßen
  • Juergen Debus
  • Thomas Schnabel
  • Barry S Rosenstein
  • Frederik Wenz
  • Odilia Popanda
  • Jenny Chang-Claude

Abstract

PURPOSE: To identify single-nucleotide polymorphisms (SNPs) in oxidative stress-related genes associated with risk of late toxicities in breast cancer patients receiving radiation therapy.

METHODS AND MATERIALS: Using a 2-stage design, 305 SNPs in 59 candidate genes were investigated in the discovery phase in 753 breast cancer patients from 2 prospective cohorts from Germany. The 10 most promising SNPs in 4 genes were evaluated in the replication phase in up to 1883 breast cancer patients from 6 cohorts identified through the Radiogenomics Consortium. Outcomes of interest were late skin toxicity and fibrosis of the breast, as well as an overall toxicity score (Standardized Total Average Toxicity). Multivariable logistic and linear regression models were used to assess associations between SNPs and late toxicity. A meta-analysis approach was used to summarize evidence.

RESULTS: The association of a genetic variant in the base excision repair gene XRCC1, rs2682585, with normal tissue late radiation toxicity was replicated in all tested studies. In the combined analysis of discovery and replication cohorts, carrying the rare allele was associated with a significantly lower risk of skin toxicities (multivariate odds ratio 0.77, 95% confidence interval 0.61-0.96, P=.02) and a decrease in Standardized Total Average Toxicity scores (-0.08, 95% confidence interval -0.15 to -0.02, P=.016).

CONCLUSIONS: Using a stage design with replication, we identified a variant allele in the base excision repair gene XRCC1 that could be used in combination with additional variants for developing a test to predict late toxicities after radiation therapy in breast cancer patients.

Bibliographical metadata

Original languageEnglish
Pages (from-to)1084-1092
Number of pages9
JournalInternational Journal of Radiation: Oncology - Biology - Physics
Volume92
Issue number5
DOIs
Publication statusPublished - 1 Aug 2015