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 fibrosis and also individual radiosensitivity. METHODS AND MATERIALS: Retrospective analysis with 69 breast cancer patients treated with breast-conserving radiotherapy; total dose delivered was restricted to vary between 54 and 55Gy. Fibrosis was evaluated according to LENT/SOMA score. DNA was extracted from blood samples; cellular radiosensitivity was measured using the G0 assay and polymorphisms by PCR-RFLP and MALDI-TOF, respectively. RESULTS: Twenty-five percent of all patients developed fibrosis of grade 2 or 3. This proportion tends to be higher in patients being polymorphic in TGFB1 or XRCC1 when compared to patients with wildtype genotype, whereas for ATM, GSTP1, SOD2 and XPD the polymorphic genotype appears to be associated with a lower risk of fibrosis. However, none of these associations are significant. In contrast, when a risk score is calculated based on all risk alleles, there was significant association with an increased risk of fibrosis (per risk allele odds ratio (ORs)=2.09, 95% confidence interval (CI): 1.32-3.55, p=0.0005). All six polymorphisms were found to have no significant effect on cellular radiosensitivity. CONCLUSIONS: It is most likely that risk for radiation-induced fibrosis can be assessed by a combination of risk alleles. This finding needs to be replicated in further studies.
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 fibrosis and also individual radiosensitivity. METHODS AND MATERIALS: Retrospective analysis with 69 breast cancerpatients treated with breast-conserving radiotherapy; total dose delivered was restricted to vary between 54 and 55Gy. Fibrosis was evaluated according to LENT/SOMA score. DNA was extracted from blood samples; cellular radiosensitivity was measured using the G0 assay and polymorphisms by PCR-RFLP and MALDI-TOF, respectively. RESULTS: Twenty-five percent of all patients developed fibrosis of grade 2 or 3. This proportion tends to be higher in patients being polymorphic in TGFB1 or XRCC1 when compared to patients with wildtype genotype, whereas for ATM, GSTP1, SOD2 and XPD the polymorphic genotype appears to be associated with a lower risk of fibrosis. However, none of these associations are significant. In contrast, when a risk score is calculated based on all risk alleles, there was significant association with an increased risk of fibrosis (per risk allele odds ratio (ORs)=2.09, 95% confidence interval (CI): 1.32-3.55, p=0.0005). All six polymorphisms were found to have no significant effect on cellular radiosensitivity. CONCLUSIONS: It is most likely that risk for radiation-induced fibrosis can be assessed by a combination of risk alleles. This finding needs to be replicated in further studies.
Authors: Aaron J Grossberg; Xiudong Lei; Ting Xu; Simona F Shaitelman; Karen E Hoffman; Elizabeth S Bloom; Michael C Stauder; Welela Tereffe; Pamela J Schlembach; Wendy A Woodward; Thomas A Buchholz; Benjamin D Smith Journal: JAMA Oncol Date: 2018-12-01 Impact factor: 31.777
Authors: Surya Rednam; Michael E Scheurer; Adekunle Adesina; Ching C Lau; Mehmet Fatih Okcu Journal: Pediatr Blood Cancer Date: 2012-10-12 Impact factor: 3.167
Authors: Chris R Kelsey; Isabel L Jackson; Scott Langdon; Kouros Owzar; Jessica Hubbs; Zeljko Vujaskovic; Shiva Das; Lawrence B Marks Journal: Clin Lung Cancer Date: 2013-01-10 Impact factor: 4.785
Authors: Gillian C Barnett; Rebecca M Elliott; Jan Alsner; Christian N Andreassen; Osama Abdelhay; Neil G Burnet; Jenny Chang-Claude; Charlotte E Coles; Sara Gutiérrez-Enríquez; Maria J Fuentes-Raspall; Maria C Alonso-Muñoz; Sarah Kerns; Annette Raabe; R Paul Symonds; Petra Seibold; Chris J Talbot; Frederik Wenz; Jennifer Wilkinson; John Yarnold; Alison M Dunning; Barry S Rosenstein; Catharine M L West; Søren M Bentzen Journal: Radiother Oncol Date: 2012-11-28 Impact factor: 6.280