XRCC1 Polymorphism Associated With Late Toxicity After Radiation Therapy in Breast Cancer Patients
Petra Seibold
(1)
,
Sabine Behrens
(1)
,
Peter Schmezer
(1)
,
Irmgard Helmbold
(1)
,
Gillian Barnett
(2)
,
Charlotte Coles
(2)
,
John Yarnold
(3)
,
Christopher Talbot
(4)
,
Takashi Imai
(5)
,
David Azria
(6, 7)
,
C. Anne Koch
(8)
,
Alison Dunning
(9)
,
Neil Burnet
(2)
,
Judith Bliss
,
R. Paul Symonds
(4)
,
Tim Rattay
(4)
,
Tomo Suga
(5)
,
Sarah Kerns
(10)
,
Céline Bourgier
(6, 7)
,
Katherine Vallis
(11)
,
Marie-Luise Sautter-Bihl
,
Johannes Classen
,
Juergen Debus
(12)
,
Thomas Schnabel
,
Barry Rosenstein
(10)
,
Frederik Wenz
(12)
,
Catharine West
(13)
,
Odilia Popanda
(1)
,
Jenny Chang-Claude
(1)
1
DKFZ -
German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg]
2 CUH - Cambridge University Hospitals - NHS
3 NHS Foundation Trust [London]
4 University of Leicester
5 NIRS - National Institute of Radiological Sciences
6 IRCM - U1194 Inserm - UM - Institut de Recherche en Cancérologie de Montpellier
7 ICM - Institut régional de Cancérologie de Montpellier
8 University Health Network [Toronto, ON, Canada]
9 CAM - University of Cambridge [UK]
10 MSSM - Icahn School of Medicine at Mount Sinai [New York]
11 University of Oxford
12 University of Heidelberg, Medical Faculty
13 MAHSC - Manchester Academic Health Science Centre
2 CUH - Cambridge University Hospitals - NHS
3 NHS Foundation Trust [London]
4 University of Leicester
5 NIRS - National Institute of Radiological Sciences
6 IRCM - U1194 Inserm - UM - Institut de Recherche en Cancérologie de Montpellier
7 ICM - Institut régional de Cancérologie de Montpellier
8 University Health Network [Toronto, ON, Canada]
9 CAM - University of Cambridge [UK]
10 MSSM - Icahn School of Medicine at Mount Sinai [New York]
11 University of Oxford
12 University of Heidelberg, Medical Faculty
13 MAHSC - Manchester Academic Health Science Centre
Alison Dunning
- Fonction : Auteur
- PersonId : 797107
- ORCID : 0000-0001-6651-7166
Judith Bliss
- Fonction : Auteur
Katherine Vallis
- Fonction : Auteur
- PersonId : 794236
- ORCID : 0000-0003-4672-5683
Marie-Luise Sautter-Bihl
- Fonction : Auteur
Johannes Classen
- Fonction : Auteur
Thomas Schnabel
- Fonction : Auteur
Résumé
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.