Format

Send to

Choose Destination
Int J Radiat Oncol Biol Phys. 2015 Aug 1;92(5):1084-1092. doi: 10.1016/j.ijrobp.2015.04.011. Epub 2015 Apr 11.

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

Author information

1
Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
2
Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center, Heidelberg, Germany.
3
Department of Oncology, Oncology Centre, Cambridge University Hospital NHS Foundation Trust, United Kingdom (UK).
4
Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, UK.
5
Department of Genetics, University of Leicester, Leicester, UK.
6
Advanced Radiation Biology Research Program, National Institute of Radiological Sciences, Chiba, Japan.
7
Department of Radiation Oncology and Medical Physics, I.C.M. - Institut regional du Cancer Montpellier, Montpellier, France.
8
Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
9
Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
10
Department of Oncology, Oncology Centre, Cambridge University Hospital NHS Foundation Trust, University of Cambridge, Cambridge, UK.
11
The Institute of Cancer Research, Clinical Trials and Statistics Unit, Sutton, UK.
12
Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK.
13
Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NH.
14
Cancer Research UK/Medical Research Council Oxford Institute for Radiation Oncology, Oxford University, Oxford, UK.
15
Department of Radiation Oncology, Staedtisches Klinikum Karlsruhe, Karlsruhe, Germany.
16
Clinic for Radiation Therapy and Radiation Oncology, St. Vincentius-Kliniken gAG, Karlsruhe, Germany.
17
Department of Radiation Oncology, University of Heidelberg, Heidelberg, Germany.
18
Clinic for Radiotherapy and Radiation Oncology, Klinikum Ludwigshafen, Ludwigshafen am Rhein, Germany.
19
Department of Radiation Oncology, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany.
20
Institute of Cancer Sciences, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
21
Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany. Electronic address: j.chang-claude@dkfz.de.

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.

PMID:
26072091
DOI:
10.1016/j.ijrobp.2015.04.011
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center