Association of transforming growth factor beta-1 single nucleotide polymorphisms with radiation-induced damage to normal tissues in breast cancer patients.
OBJECTIVE
To investigate whether transforming growth factor beta-1 (TGFbeta1) single nucleotide polymorphisms were associated with the susceptibility of breast cancer patients to severe radiation-induced normal tissue damage.


METHODS
PCR-RFLP assays were performed for TGFbeta1 gene polymorphisms on DNA obtained from 103 breast cancer patients who received radiotherapy. The G-800A, C-509T, T+869C and G+915C polymorphic sites were examined, and genotype and allele frequencies of two subgroups of patients were calculated and compared.


RESULTS
The less prevalent -509T and +869C alleles were significantly associated with a subgroup of patients who developed severe radiation-induced normal tissue fibrosis (n=15) when compared with those who did not (n=88) (odds ratio=3.4, p=0.0036, and 2.37, p=0.035, respectively). Furthermore, patients with the -509TT or +869CC genotypes were between seven and 15 times more likely to develop severe fibrosis.


CONCLUSIONS
These findings imply a role for the -509T and +869C alleles in the pathobiological mechanisms underlying susceptibility to radiation-induced fibrosis. Their predictive value would be limited to patients who are -509TT or +869CC, but if "fibrosis-associated" polymorphic sites in other genes could be identified, it may be possible to detect fibrosis prone individuals before radiotherapy with greater certainty.
Quarmby
S
S
Department of Pathological Sciences, Stopford Building, Manchester University, Manchester M13 9PT, UK. steven.l.quarmby@man.ac.uk
Fakhoury
H
H
Levine
E
E
Barber
J
J
Wylie
J
J
Hajeer
A H
AH
West
C
C
Stewart
A
A
Magee
B
B
Kumar
S
S
D000483:Alleles; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000532:radiotherapy*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005355:Fibrosis; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011832:Radiation Injuries / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D011836:Radiation Tolerance / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1
D004273:DNA, Neoplasm; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1