Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Apr 26:7:65.
doi: 10.1186/1748-717X-7-65.

Association of single nucleotide polymorphisms in the genes ATM, GSTP1, SOD2, TGFB1, XPD and XRCC1 with risk of severe erythema after breast conserving radiotherapy

Annette Raabe  1 , Katharina Derda, Sebastian Reuther, Silke Szymczak, Kerstin Borgmann, Ulrike Hoeller, Andreas Ziegler, Cordula Petersen, Ekkehard Dikomey
Affiliations

Association of single nucleotide polymorphisms in the genes ATM, GSTP1, SOD2, TGFB1, XPD and XRCC1 with risk of severe erythema after breast conserving radiotherapy

Annette Raabe et al. Radiat Oncol. .

Abstract

Purpose: To examine the association of polymorphisms in ATM (codon 158), GSTP1 (codon 105), SOD2 (codon 16), TGFB1 (position -509), XPD (codon 751), and XRCC1 (codon 399) with the risk of severe erythema after breast conserving radiotherapy.

Methods and materials: Retrospective analysis of 83 breast cancer patients treated with breast conserving radiotherapy. A total dose of 50.4 Gy was administered, applying 1.8 Gy/fraction within 42 days. Erythema was evaluated according to the Radiation Therapy Oncology Group (RTOG) score. DNA was extracted from blood samples and polymorphisms were determined using either the Polymerase Chain Reaction based Restriction-Fragment-Length-Polymorphism (PCR-RFL) technique or Matrix-Assisted-Laser-Desorption/Ionization -Time-Of-Flight-Mass-Spectrometry (MALDI-TOF). Relative excess heterozygosity (REH) was investigated to check compatibility of genotype frequencies with Hardy-Weinberg equilibrium (HWE). In addition, p-values from the standard exact HWE lack of fit test were calculated using 100,000 permutations. HWE analyses were performed using R.

Results: Fifty-six percent (46/83) of all patients developed erythema of grade 2 or 3, with this risk being higher for patients with large breast volume (odds ratio, OR = 2.55, 95% confidence interval, CI: 1.03-6.31, p = 0.041). No significant association between SNPs and risk of erythema was found when all patients were considered. However, in patients with small breast volume the TGFB1 SNP was associated with erythema (p = 0.028), whereas the SNP in XPD showed an association in patients with large breast volume (p = 0.046). A risk score based on all risk alleles was neither significant in all patients nor in patients with small or large breast volume. Risk alleles of most SNPs were different compared to a previously identified risk profile for fibrosis.

Conclusions: The genetic risk profile for erythema appears to be different for patients with small and larger breast volume. This risk profile seems to be specific for erythema as compared to a risk profile for fibrosis.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Incidence of breast erythema in 83 patients treated by breast conserving radiotherapy. Data are stratified for a breast volume of 750 cm³. Grade of erythema was determined using the RTOG score.
Figure 2
Figure 2
Association of SNPs in ATM, GSTP1, TGFB1, XPD and XRCC1 with risk of either erythema or fibrosis for breast cancer patients treated by conserving radiotherapy. Odd ratios (ORs) obtained are plotted vs. the respective gene variants. Data shown for fibrosis are taken from [22].
See this image and copyright information in PMC

References

    1. Jung H, Beck-Bornholdt HP, Svoboda V, Alberti W, Herrmann T. Quantification of late complications after radiation therapy. Radiother Oncol. 2001;61:233–246. doi: 10.1016/S0167-8140(01)00457-1. - DOI - PubMed
    1. Ko C, Citrin D. Radiotherapy for the management of locally advanced squamous cell carcinoma of the head and neck. Oral Dis. 2009;15:121–132. doi: 10.1111/j.1601-0825.2008.01495.x. - DOI - PMC - PubMed
    1. Baumann M, Herrmann T, Koch R, Matthiessen W, Appold S, Wahlers B, Kepka L, Marschke G, Feltl D, Fietkau R. et al.Final results of the randomized phase III CHARTWEL-trial (ARO 97–1) comparing hyperfractionated-accelerated versus conventionally fractionated radiotherapy in non-small cell lung cancer (NSCLC) Radiother Oncol. 2011;100:76–85. doi: 10.1016/j.radonc.2011.06.031. - DOI - PubMed
    1. Hatton M, Nankivell M, Lyn E, Falk S, Pugh C, Navani N, Stephens R, Parmar M. Induction chemotherapy and continuous hyperfractionated accelerated radiotherapy (chart) for patients with locally advanced inoperable non-small-cell lung cancer: the MRC INCH randomized trial. Int J Radiat Oncol Biol Phys. 2011;81:712–718. doi: 10.1016/j.ijrobp.2010.06.053. - DOI - PubMed
    1. Turesson I, Nyman J, Holmberg E, Oden A. Prognostic factors for acute and late skin reactions in radiotherapy patients. Int J Radiat Oncol Biol Phys. 1996;36:1065–1075. doi: 10.1016/S0360-3016(96)00426-9. - DOI - PubMed

Publication types

MeSH terms