Genetic prediction of RT induced morbidityTGFβ1 SNPs and radio-induced toxicity in prostate cancer patients
Section snippets
Patients
Samples for this epidemiological study were obtained from 413 unselected Galician (NW Spain) prostate cancer patients, treated at the Radiation Oncology Department of the Clinical University Hospital of Santiago de Compostela (Spain) from 2006 to 2009. All the patients were recruited into the RADIOGEN study, which was started in 2005 as a collection of blood, dosimetric data as well as clinical and toxicity data from prostate cancer patients treated with 3D-CRT. Written informed consent was
Results
A total of 413 patients accepted to participate in the study. Patient and tumour characteristics are outlined in Supplementary Table 2. Neither tumour stage nor baseline patient clinical features were correlated with the risk of developing late toxicity.
Late toxicity data were available for all participants (Table 1). Thirty-eight (9.2%) of these developed gastrointestinal morbidity, while 63 (15.25%) suffered from genitourinary morbidity. Follow-up mean was 32 months (range 24–122) (
Discussion
Our study did not detect any evidence of association between the TGFβ1 SNPs rs1800469, rs1800470 and rs1800472 and gastrointestinal or genitourinary late radiotherapy toxicities.
We are conscious about one of the limitations of our study that is the follow up is currently 2 years. However, there is evidence to suggest that the outcome at 2 years predicts for late normal-tissue toxicity at 5 years after radiotherapy [27].
Previous studies had reported that rs1800469, located on the promoter region of
Conflict of interest
The authors declare that they have no conflict of interest.
Acknowledgements
We are grateful to all participating patients for their cooperation. L.F. is supported by the Isabel Barreto programme from Xunta de Galicia and Fondo Social Europeo. This work was funded by a grant from the Instituto de Salud Carlos III (FIS PI10/00164) and Fondo Europeo de Desarrollo Regional (FEDER 2007-2013).
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A genome wide association study (GWAS) providing evidence of an association between common genetic variants and late radiotherapy toxicity
2014, Radiotherapy and OncologyCitation Excerpt :Replication of the most significant associations identified in RAPPER was carried out in cohorts from the Radiogenomics Consortium (RGC) with late toxicity data available. This included 1378 prostate cancer patients with 2-year toxicity data: 516 patients treated with conformal radical or post-prostatectomy radiotherapy at the Clinical University Hospital of Santiago de Compostela, Spain, in the RADIOGEN trial [17,18], and 862 treated with brachytherapy with or without additional external beam radiotherapy at Mount Sinai Hospital, in the Gene-PARE study [2,3]. Replication was also carried out in 355 breast cancer patients from the LeND study [8,19].
Evaluating the role of mitochondrial DNA variation to the genetic predisposition to radiation-induced toxicity
2014, Radiotherapy and OncologyCitation Excerpt :Samples were obtained from 606 consecutive Galician (NW Spain) prostate cancer patients, treated with three-dimensional conformational radiotherapy (3D-CRT) as previously described (RADIOGEN study [20,21]) at the Radiation Oncology Department of the Clinical University Hospital of Santiago de Compostela (Spain) from 2006 to 2011.
Single-nucleotide polymorphisms studied for associations with urinary toxicity from <sup>125</sup>I prostate brachytherapy implants
2014, BrachytherapyCitation Excerpt :Recently, a study identified two SNPs on the TGFβ1 gene that were associated with the occurrence of acute nocturia in 322 men treated with intensity-modulated radiation therapy for their prostate cancer (19). These studies are in contrast to several studies that have failed to identify SNPs associated with urinary toxicity (9, 20, 21). Some earlier studies using candidate SNPs had even grouped rectal and/or urinary toxicity together to identify promising SNPs (7, 11, 22).
Finding the Genetic Determinants of Adverse Reactions toRadiotherapy
2014, Clinical OncologyCitation Excerpt :Combined data from two British cohorts published at the same time showed a significant association of the −509 T allele with fibrosis [42,57], whereas a further study showed an association with the 869 T > C allele [43]. More recently, the large British RAPPER cohort of breast and prostate cancer patients and a cohort of Spanish prostate cancer patients failed to confirm any association of TGFB1 genotypes with radiation toxicity [58,59]. This negative finding was further substantiated in a meta-analysis of 2782 participants from 11 cohorts [60].