Genetic prediction of RT induced morbidity
TGFβ1 SNPs and radio-induced toxicity in prostate cancer patients

https://doi.org/10.1016/j.radonc.2012.01.015Get rights and content

Abstract

Background and purpose

We have performed a case-control study in 413 prostate cancer patients to test for association between TGFβ1 and the development of late normal-tissue toxicity among prostate cancer patients treated with three-dimensional conformational radiotherapy (3D-CRT)

Materials and methods

Late gastrointestinal and genitourinary toxicities were assessed for at least two years after radiotherapy in 413 patients according to CTCAEvs3 scores. Codominant genotypic tests and haplotypic analyses were undertaken to evaluate the correlation between TGFβ1 SNPs rs1800469, rs1800470 and rs1800472 and radio-induced toxicity.

Results

Neither the SNPs nor the haplotypes were found to be associated with the risk of late toxicity.

Conclusions

We were able to exclude up to a 2-fold increase in the risk of developing late gastrointestinal and genitourinary radio-induced toxicity due to the TGFβ1 SNPs rs1800469 and rs1800470, as well as the two most frequent TGFβ1 haplotypes.

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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