Genetic predictors of adverse radiotherapy effects: the Gene-PARE project.
OBJECTIVE
The development of adverse effects resulting from the radiotherapy of cancer limits the use of this treatment modality. The validation of a test capable of predicting which patients would be most likely to develop adverse responses to radiation treatment, based on the possession of specific genetic variants, would therefore be of value. The purpose of the Genetic Predictors of Adverse Radiotherapy Effects (Gene-PARE) project is to help achieve this goal.


METHODS
A continuously expanding biorepository has been created consisting of frozen lymphocytes and DNA isolated from patients treated with radiotherapy. In conjunction with this biorepository, a database is maintained with detailed clinical information pertaining to diagnosis, treatment, and outcome. The DNA samples are screened using denaturing high performance liquid chromatography (DHPLC) and the Surveyor nuclease assay for variants in ATM, TGFB1, XRCC1, XRCC3, SOD2, and hHR21. It is anticipated that additional genes that control the biologic response to radiation will be screened in future work.


RESULTS
Evidence has been obtained that possession of variants in genes, the products of which play a role in radiation response, is predictive for the development of adverse effects after radiotherapy.


CONCLUSIONS
It is anticipated that the Gene-PARE project will yield information that will allow radiation oncologists to use genetic data to optimize treatment on an individual basis.
Ho
Alice Y
AY
Department of Radiation Oncology, Mount Sinai School of Medicine, New York, NY, USA.
Atencio
David P
DP
Peters
Sheila
S
Stock
Richard G
RG
Formenti
Silvia C
SC
Cesaretti
Jamie A
JA
Green
Sheryl
S
Haffty
Bruce
B
Drumea
Karen
K
Leitzin
Larisa
L
Kuten
Abraham
A
Azria
David
D
Ozsahin
Mahmut
M
Overgaard
Jens
J
Andreassen
Christian N
CN
Trop
Cynthia S
CS
Park
Janelle
J
Rosenstein
Barry S
BS
D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004268:DNA-Binding Proteins / Q000235:genetics; D003850:Deoxyribonuclease I / Q000032:analysis; D006801:Humans; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000532:radiotherapy; D009687:Nuclear Proteins / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011237:Predictive Value of Tests; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011832:Radiation Injuries / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics*; D011878:Radiotherapy / Q000009:adverse effects*; D013482:Superoxide Dismutase / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1; D025521:Tumor Suppressor Proteins / Q000235:genetics; D000076105:X-ray Repair Cross Complementing Protein 1; D000099156:Superoxide Dismutase 2
D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D003850:Deoxyribonuclease I; D009687:Nuclear Proteins; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D013482:Superoxide Dismutase; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D025521:Tumor Suppressor Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; D000099156:Superoxide Dismutase 2; C429022:RAD21 protein, human; C508960:TGFB1 protein, human; C000619371:XRCC1 protein, human; C576324:ATM protein, human