Association of polymorphisms in TGFB1, XRCC1, XRCC3 genes and CD8 T-lymphocyte apoptosis with adverse effect of radiotherapy for prostate cancer.
Emina MališićNina PetrovićMuriel BrenguesDavid AzriaIvana Z MatićIvana Srbljak ĆukKatarina KopčalićTatjana StanojkovićMarina NikitovićPublished in: Scientific reports (2022)
The genetic background of each person might affect the severity of radiotherapy (RT)-induced normal tissue toxicity. The aim of study was to evaluate the influence of TGFB1 C-509T and Leu10Pro, XRCC1 Arg280His and XRCC3 Thr241Met polymorphisms as well as the level of radiation-induced CD8 T-lymphocyte apoptosis (RILA) on adverse effects of RT for prostate cancer (PCa). The study included 88 patients with localized or locally advanced PCa who were treated with RT. The polymorphisms were determined by PCR-RFLP analysis on DNA from peripheral blood mononuclear cells. RILA values were measured by flow cytometry. We found that CT genotype of TGFB1 C-509T could be protective biomarker for acute genitourinary (GU) and gastrointestinal (GI) radiotoxicity, while Thr variant of XRCC3 Thr241Met could predict the risk for acute GU radiotoxicity. Correlation between RILA values and toxicity was not detected. Univariate logistic regression analysis showed that Gleason score and risk group were risk factors for late GU, while for late GI radiotoxicity it was diabetes mellitus type 2. However, in multivariate model those were not proven to be significant and independent risk factors. Identification of assays combination predicting individual radiosensitivity is a crucial step towards personalized RT approach.
Keyphrases
- prostate cancer
- radiation induced
- dna repair
- locally advanced
- oxidative stress
- radical prostatectomy
- radiation therapy
- flow cytometry
- risk factors
- liver failure
- early stage
- squamous cell carcinoma
- drug induced
- dna damage
- endoplasmic reticulum stress
- respiratory failure
- cell death
- type diabetes
- magnetic resonance imaging
- gene expression
- cell cycle arrest
- high glucose
- emergency department
- lymph node
- metabolic syndrome
- data analysis
- diabetic rats
- transcription factor
- signaling pathway
- insulin resistance
- weight loss
- pi k akt
- skeletal muscle
- acute respiratory distress syndrome