Association of transforming growth factor beta-1 single nucleotide polymorphisms with radiation-induced damage to normal tissues in breast cancer patients

Abstract

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.

No association between SNPs regulating TGF-β1 secretion and late radiotherapy toxicity to the breast: Results from the RAPPER study

“…This large, purpose designed study has been unable to confirm recent reports of significant associations between the TGFB1 (C-509T) SNP and increased risk of radiation fibrosis [20][21][22]. We did not find a significant association between either of the correlated TGFB1 SNPs, L10P (rs1800470) or C-509T (rs1800469), with the development of induration, assessed by the clinician.…”

“…However, these results were not replicated in a further study by the same group [39]. In a combined analysis of two published studies [20,22] of adjuvant radiotherapy to the breast (a total of 236 patients) it was reported that CT heterozygotes for C-509T had a 3-fold increased risk and TT homozygotes had a 15-fold increased risk of fibrosis following radiotherapy compared with CC homozygotes [22].…”

“…However, others have not found such associations [19]. Several small studies have reported a correlation between SNPs in the TGFB1 gene and fibrosis, one form of late radiotherapy toxicity, in breast cancer patients [20][21][22]. In addition, a study of prostate cancer patients found significant associations between TGF genotype and certain toxicity end-points [23].…”

Can cutaneous telangiectasiae as late normal-tissue injury predict cardiovascular disease in women receiving radiotherapy for breast cancer?

“…This scale provides both subjective and objective analyses and a detailed and specific description of the nature (phenotype) and severity of the injury(s) that are individually scored. Results showed that homozygosity (TT) for the TGFb1 (C-509T) gene promoter polymorphism confers a 15-fold increased risk of fibrosis after radiotherapy (P ¼ 3x10 À6 ) compared with (CC) homozygotes, thus confirming previous independent analyses (Quarmby et al, 2003;Andreassen et al, 2005). In addition, a 15 Gy electron boost and/or the inheritance of X-ray repair crosscomplementing 1 (XRCC1) (R399Q) SNP contributed to the risk of telangiectasiae.…”

“…Previous studies have shown potential common genetic and radiobiological pathways involved in the development of late normal-tissue complications after radiotherapy (Quarmby et al, 2003;Andreassen et al, 2005;Giotopoulos et al, 2007). A potential genotypic association between cutaneous telangiectasiae and the development of RIHD would be intriguing as it may confer a number of clinical implications.…”