Impact of TGFB1 Leu10Pro polymorphism on acute radiotherapy-induced toxicity in prostate cancer patients

Abstract

Background: Radiotherapy (RT)-induced acute toxicity associated with bladder and bowel injury has great impact the quality of life for prostate cancer (PCa) patients. TGFB1 is a key proinflammatory and profibrotic cytokine, but its role in acute toxicity is still unclear. TGFB1 T>C transition at codon 10 results in leucine to proline substitution and increased TGFB1 protein levels. The aim of this study was to examine impact of TGFB1 Leu10Pro (rs1800470) polymorphism on RT-induced acute toxicity in PCa patients. Patients and methods: Eighty two patients who had a localized or locally advanced PCa were treated with radical (72 Gy)(n=47) or postoperative/salvage (66 Gy)(n=35) RT without previous hormonal therapy. TGFB1 Leu10Pro was determined by PCR-RFLP analysis on DNA from PBMC. The differences in the distribution of genotypes for dominant, recessive, codominant and overdominant genetic model between patients with or without acute genitourinary (GU) or gastrointestinal (GI) toxicity as well as different grade of toxicity were tested by χ2 and Fisher’s exact test. P values ≤0.05 were considered statistically significant. Results: Heterozygote PCa patients had lower rate of acute GU and GI toxicity then homozygotes (LeuLeu, LeuPro, ProPro were: 100%, 90.7%, 100% for GU and 92.0%, 88.4%, 100%, respectively for GI). The frequency of toxicity grade ≥2 were higher in LeuPro then both homozygote carriers (41% vs. 28.2% for GU and 26.3% vs. 21.6% for GI acute toxicity). The differences were not statistically significant. Conclusion: The present study did not establish impact of TGFB1 Leu10Pro polymorphism on RT-induced acute toxicity in PCa patients.5th Congress of the Serbian Association for Cancer Research with International Participation SDIR-5, Virtual event, December 3, Belgrade, 2021

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