Association of transforming growth factor beta-1 single nucleotide polymorphisms with radiation-induced damage to normal tissues in breast cancer patients.
AuthorsQuarmby, Steven L
Wylie, James P
Hajeer, A H
West, Catharine M L
Stewart, Alan L
AffiliationDepartment of Pathological Sciences, Stopford Building, Manchester University, Manchester M13 9PT, UK. firstname.lastname@example.org
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AbstractPURPOSE: 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. MATERIALS AND 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.
CitationAssociation of transforming growth factor beta-1 single nucleotide polymorphisms with radiation-induced damage to normal tissues in breast cancer patients. 2003, 79 (2):137-43 Int. J. Radiat. Biol.
JournalInternational Journal of Radiation Biology
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