Genetic polymorphisms in DNA repair and damage response genes and late normal tissue complications of radiotherapy for breast cancer
Open Access
- 14 April 2009
- journal article
- Published by Springer Science and Business Media LLC in British Journal of Cancer
- Vol. 100 (10), 1680-1686
- https://doi.org/10.1038/sj.bjc.6605036
Abstract
Breast-conserving surgery followed by radiotherapy is effective in reducing recurrence; however, telangiectasia and fibrosis can occur as late skin side effects. As radiotherapy acts through producing DNA damage, we investigated whether genetic variation in DNA repair and damage response confers increased susceptibility to develop late normal skin complications. Breast cancer patients who received radiotherapy after breast-conserving surgery were examined for late complications of radiotherapy after a median follow-up time of 51 months. Polymorphisms in genes involved in DNA repair (APEX1, XRCC1, XRCC2, XRCC3, XPD) and damage response (TP53, P21) were determined. Associations between telangiectasia and genotypes were assessed among 409 patients, using multivariate logistic regression. A total of 131 patients presented with telangiectasia and 28 patients with fibrosis. Patients with variant TP53 genotypes either for the Arg72Pro or the PIN3 polymorphism were at increased risk of telangiectasia. The odds ratios (OR) were 1.66 (95% confidence interval (CI): 1.02–2.72) for 72Pro carriers and 1.95 (95% CI: 1.13–3.35) for PIN3 A2 allele carriers compared with non-carriers. The TP53 haplotype containing both variant alleles was associated with almost a two-fold increase in risk (OR 1.97, 95% CI: 1.11–3.52) for telangiectasia. Variants in the TP53 gene may therefore modify the risk of late skin toxicity after radiotherapy.Keywords
This publication has 50 references indexed in Scilit:
- Effects of common germline genetic variation in cell cycle control genes on breast cancer survival: results from a population-based cohortBreast Cancer Research, 2008
- Variability: The common factor linking low dose-induced genomic instability, adaptation and bystander effectsMutation Research - Reviews in Mutation Research, 2007
- The late radiotherapy normal tissue injury phenotypes of telangiectasia, fibrosis and atrophy in breast cancer patients have distinct genotype-dependent causesBritish Journal of Cancer, 2007
- Predictive factors for late normal tissue complications following radiotherapy for breast cancerBreast Cancer Research and Treatment, 2007
- The XRCC1 -77T->C variant: haplotypes, breast cancer risk, response to radiotherapy and the cellular response to DNA damageCarcinogenesis: Integrative Cancer Research, 2006
- Association between TP53 and p21 genetic polymorphisms and acute side effects of radiotherapy in breast cancer patientsBreast Cancer Research and Treatment, 2005
- Dual effect of p53 on radiation sensitivity in vivo: p53 promotes hematopoietic injury, but protects from gastro-intestinal syndrome in miceOncogene, 2004
- The role of p53 in determining sensitivity to radiotherapyNature Reviews Cancer, 2003
- Cosmetic Outcome and Breast Morbidity in Breast-Conserving TreatmentActa Oncologica, 2002
- Prognostic factors for acute and late skin reactions in radiotheraphy patientsInternational Journal of Radiation Oncology*Biology*Physics, 1996