Germline glutathione S-transferase variants in breast cancer: relation to diagnosis and cutaneous long-term adverse effects after two fractionation patterns of radiotherapy.
OBJECTIVE
To explore whether certain glutathione S-transferase (GST) polymorphisms are associated with an increased risk of breast cancer or the level of radiation-induced adverse effects after two fractionation patterns of adjuvant radiotherapy.


METHODS
The prevalence of germline polymorphic variants in GSTM1, GSTP1, and GSTT1 was determined in 272 breast cancer patients and compared with that in a control group of 270 women from the general population with no known history of breast cancer. The genetic variants were determined using multiplex polymerase chain reaction followed by restriction enzyme fragment analysis. In 253 of the patients surveyed for radiotherapy-induced side effects after a median observation time of 13.7 years (range, 7-22.8 years), the genotypes were related to the long-term effects observed after two fractionation patterns (treatment A, 4.3 Gy in 10 fractions for 156 patients; and treatment B, 2.5 Gy in 20 fractions for 97; both administered within a 5-week period).


RESULTS
None of the GST polymorphisms conferred an increased risk of breast cancer, either alone or in combination. Compared with treatment B, treatment A was followed by an increased level of moderate to severe radiation-induced side effects for all the endpoints studied (i.e., degree of telangiectasia, subcutaneous fibrosis and atrophy, lung fibrosis, costal fractures, and pleural thickening; p <0.001 for all endpoints). A significant association was found between the level of pleural thickening and the GSTP1 Ile105Val variant.


CONCLUSIONS
The results of this study have illustrated the impact of hypofractionation on the level of adverse effects and indicated that the specific alleles of GSTP1, M1, and T1 studied here may be significant in determining the level of adverse effects after radiotherapy.
Edvardsen
Hege
H
Department of Genetics, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet Medical Centre, Oslo, Norway. Hege.Edvardsen@rr-research.no
Kristensen
Vessela N
VN
Grenaker Alnaes
Grethe Irene
GI
Bøhn
Mona
M
Erikstein
Bjørn
B
Helland
Aslaug
A
Børresen-Dale
Anne-Lise
AL
Fosså
Sophie Dorothea
SD
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000532:radiotherapy / Q000601:surgery; D016022:Case-Control Studies; D019583:Dose Fractionation, Radiation; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000201:enzymology / Q000528:radiation effects; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects
D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1