TY - JOUR
T1 - Association of single nucleotide polymorphisms in ATM, GSTP1, SOD2, TGFB1, XPD and XRCC1 with clinical and cellular radiosensitivity
AU - Zschenker, Oliver
AU - Raabe, Annette
AU - Boeckelmann, Inga Kathleen
AU - Borstelmann, Sonko
AU - Szymczak, Silke
AU - Wellek, Stefan
AU - Rades, Dirk
AU - Hoeller, Ulrike
AU - Ziegler, Andreas
AU - Dikomey, Ekkehard
AU - Borgmann, Kerstin
PY - 2010/10/1
Y1 - 2010/10/1
N2 - 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 55 Gy. 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.
AB - 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 55 Gy. 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.
UR - http://www.scopus.com/inward/record.url?scp=77957877713&partnerID=8YFLogxK
U2 - 10.1016/j.radonc.2010.01.016
DO - 10.1016/j.radonc.2010.01.016
M3 - Journal articles
C2 - 20170971
AN - SCOPUS:77957877713
SN - 0167-8140
VL - 97
SP - 26
EP - 32
JO - Radiotherapy and Oncology
JF - Radiotherapy and Oncology
IS - 1
ER -
