TGFbeta1 polymorphisms and late clinical radiosensitivity in patients treated for gynecologic tumors.
OBJECTIVE
To investigate the association between six transforming growth factor beta1 gene (TGFbeta1) polymorphisms (-1.552delAGG, -800G>A, -509C>T, Leu10Pro, Arg25Pro, Thr263Ile) and the occurrence of late normal tissue reactions after gynecologic radiotherapy (RT).


METHODS
Seventy-eight women with cervical or endometrial cancer and 140 control individuals were included in the study. According to the Common Terminology Criteria for Adverse Events version 3.0 (CTCAEv3.0) scale, 25 patients showed late adverse RT reactions (CTC2+), of whom 11 had severe complications (CTC3+). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), single base extension and genotyping assays were performed to examine the polymorphic sites in TGFbeta1.


RESULTS
Homozygous variant -1.552delAGG, -509TT, and 10Pro genotypes were associated with the risk of developing late severe RT reactions. Triple (variant) homozygous patients had a 3.6 times increased risk to develop severe RT reactions (p=0.26). Neither the -800A allele, nor the 25Pro allele or the 263Ile allele were associated with clinical radiosensitivity. There was perfect linkage disequilibrium (LD) between the -1.552delAGG and the -509C>T polymorphisms, and tight LD between the -1.552/-509 and the Leu10Pro polymorphisms. Haplotype analysis revealed two major haplotypes but could not distinguish radiosensitive from nonradiosensitive patients.


CONCLUSIONS
The present study shows that homozygous variant TGFbeta1 -1.552delAGG, -509TT, and 10Pro genotypes may be associated with severe clinical radiosensitivity after gynecologic RT.
De Ruyck
Kim
K
Department of Anatomy, Embryology, Histology and Medical Physics, Ghent University, and Department of Radiation Oncology, Gent University Hospital, Belgium. kim.deruyck@UGent.be
Van Eijkeren
Marc
M
Claes
Kathleen
K
Bacher
Klaus
K
Vral
Anne
A
De Neve
Wilfried
W
Thierens
Hubert
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016001:Confidence Intervals; D016889:Endometrial Neoplasms / Q000235:genetics / Q000532:radiotherapy*; D005260:Female; D006720:Homozygote; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011832:Radiation Injuries / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000532:radiotherapy*
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1