No association between SNPs regulating TGF-β1 secretion and late radiotherapy toxicity to the breast: results from the RAPPER study.
OBJECTIVE
Several small studies have reported associations between TGFB1 single nucleotide polymorphisms (SNPs), considered to increase secretion of TGF-β1, and greater than 3-fold increases in incidence of fibrosis - an indicator of late toxicity after radiotherapy in breast cancer patients.


METHODS
Two SNPs in TGFB1, C-509T (rs1800469) and L10P (rs1800470), were genotyped in 778 breast cancer patients who had received radiotherapy to the breast. Late radiotherapy toxicity was assessed two years after radiotherapy using a validated photographic technique, clinical assessment and patient questionnaires.


RESULTS
On photographic assessment, 210 (27%) patients showed some degree of breast shrinkage, whilst 45 (6%) patients showed marked breast shrinkage. There was no significant association of genotype at either of the TGFB1 SNPs with any measure of late radiation toxicity.


CONCLUSIONS
This adequately powered trial failed to confirm previously reported increases in fibrosis with TGFB1 genotype - any increase greater than 1.36 can be excluded with 95% confidence. Similar frequent failures to replicate associations with candidate genes have been resolved using genome-wide association scans: this methodology detects common, low risk alleles but requires even larger patient numbers for adequate statistical power.
Barnett
Gillian C
GC
Department of Oncology, University of Cambridge, Cambridge, UK. gillbarnett@doctors.org.uk
Coles
Charlotte E
CE
Burnet
Neil G
NG
Pharoah
Paul D P
PD
Wilkinson
Jennifer
J
West
Catharine M L
CM
Elliott
Rebecca M
RM
Baynes
Caroline
C
Dunning
Alison M
AM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics* / Q000532:radiotherapy*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000532:radiotherapy*; D016009:Chi-Square Distribution; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005355:Fibrosis / Q000209:etiology / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D010781:Photography; D020641:Polymorphism, Single Nucleotide; D011832:Radiation Injuries / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics*; D011878:Radiotherapy / Q000009:adverse effects*; D011795:Surveys and Questionnaires; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1