PO-0940 A TGFB1 SNP ASSOCIATED WITH QUALITY OF LIFE IMPAIRING TOXICITY IN PROSTATE CANCER PATIENTS TREATED WITH RADIOTHERAPY

Abstract

Purpose/Objective: Acute and late side effects of radiation therapy may significantly impair patients' quality of life. Therefore the availability of predictive biomarkers is desirable and could help maximizing the therapeutic index. TGFbeta1 is proposed as a master key to initiate and promote side effects of radiation therapy. We already identified a DNA sequence variant of the TGFB1 gene (rs1800471-G>C; Arg25Pro), which was linked to radiochemotherapy related side effects in 163 patients treated for locally advanced rectal cancer. All 21 patients carrying the TGFB1 Pro25 allele experienced acute side effects CTC >= grade 2 (P=0.0006). We now tested TGFB1 gene variants in patients treated with radiotherapy for prostate cancer. Materials and Methods: 218 consecutively sampled patients, aged between 53 and 83 years with biopsy-proven prostate cancer were included. Patients had received definitive therapy with radiation doses between 64 Gy and 72 Gy, doses and PTVs were adjusted to disease stage and risk factors. Acute and late genitourinary and gastrointestinal side effects were documented according to CTC or LENT SOMA scale. Median follow-up time was 77 month; range 9 - 180 month. Nine germline polymorphisms covering the common genetic diversity in the TGFB1 gene were genotyped using the primer extension method (SNaPshot). Statistical methods applied were Fisher's exact test for variants with two or a modified X2 test for variants with three genotype configurations. Results: Overall, 25.7% and 17.4% of the patients developed acute and late side effects >= grade 2, respectively. In the analysed dose range, there was no correlation between the radiation dose level and the occurrence of side effects. Of the nine polymorphisms tested, only Arg25Pro was associated with quality of life impairing toxicity. Within the 218 patients 28 (12.8%) carried the variant Pro25 allele. Such patients had a significantly (p=0.032) higher risk for the development of late side effects (LENT SOMA >= grade 2) compared to patients carrying the wild type alleles, the odds ratio being 2,63 (CI 1,084- 6,397). For acute side effects (CTC >= grade 2) the increase of risk for patients carrying the Pro25 allele was not significant; here the odds ratio was 1,317 (CI 0.570-3.045). Conclusions: The relation between a genetic variant of the TGFB1 gene and the occurrence of radiotherapy related side effects in two independent patient cohorts, supports the importance of TGFs1 for the radiation response. Amongst others, the TGFB1 Pro25 variant could be a relevant marker for individual treatment stratification.