scholarly journals Identification of Risk Loci for Radiotoxicity in Prostate Cancer by Comprehensive Genotyping of TGFB1 and TGFBR1

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5585
Author(s):  
Manuel Guhlich ◽  
Laura Hubert ◽  
Caroline Patricia Nadine Mergler ◽  
Margret Rave-Fraenk ◽  
Leif Hendrik Dröge ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Repair ◽  
Genetic Variability ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Late Toxicity ◽  
Mechanistic Explanation ◽  
Radiation Toxicity ◽  
Repair Capacity ◽  
Dna Repair Capacity

Genetic variability in transforming growth factor beta pathway (TGFB) was suggested to affect adverse events of radiotherapy. We investigated comprehensive variability in TGFB1 (gene coding for TGFβ1 ligand) and TGFBR1 (TGFβ receptor-1) in relation to radiotoxicity. Prostate cancer patients treated with primary radiotherapy (n = 240) were surveyed for acute and late toxicity. Germline polymorphisms (n = 40) selected to cover the common genetic variability in TGFB1 and TGFBR1 were analyzed in peripheral blood cells. Human lymphoblastoid cell lines (LCLs) were used to evaluate a possible impact of TGFB1 and TGFBR1 genetic polymorphisms to DNA repair capacity following single irradiation with 3 Gy. Upon adjustment for multiplicity testing, rs10512263 in TGFBR1 showed a statistically significant association with acute radiation toxicity. Carriers of the Cytosine (C)-variant allele (n = 35) featured a risk ratio of 2.17 (95%-CI 1.41–3.31) for acute toxicity ≥ °2 compared to Thymine/Thymine (TT)-wild type individuals (n = 205). Reduced DNA repair capacity in the presence of the C-allele of rs10512263 might be a mechanistic explanation as demonstrated in LCLs following irradiation. The risk for late radiotoxicity was increased by carrying at least two risk genotypes at three polymorphic sites, including Leu10Pro in TGFB1. Via comprehensive genotyping of TGFB1 and TGFBR1, promising biomarkers for radiotoxicity in prostate cancer were identified.

scholarly journals Radiosensitivity of Prostate Cancer and BPH Patients Studied by DNA Repair Capacity, CA and FISH.

2008 ◽  
Vol 43 (5) ◽  
Author(s):  
A. Cebulska-Wasilewska ◽  
Z. Dobrowolski ◽  
Z. Rudek ◽  
M. Krzysiek ◽  
J. Miszczyk ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Repair ◽  
Repair Capacity ◽  
Dna Repair Capacity

scholarly journals Polymorphisms of Homologous RecombinationRAD51,RAD51B,XRCC2, andXRCC3Genes and the Risk of Prostate Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Maria Nowacka-Zawisza ◽  
Ewelina Wiśnik ◽  
Andrzej Wasilewski ◽  
Milena Skowrońska ◽  
Ewa Forma ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Repair ◽  
Cancer Risk ◽  
Cancer Susceptibility ◽  
Critical Role ◽  
Prostate Cancer Risk ◽  
Nucleotide Polymorphisms ◽  
Repair Capacity ◽  
Dna Repair Capacity ◽  
Risk Of Cancer

Genetic polymorphisms in DNA repair genes may induce individual variations in DNA repair capacity, which may in turn contribute to the risk of cancer developing. Homologous recombination repair (HRR) plays a critical role in maintaining chromosomal integrity and protecting against carcinogenic factors. The aim of the present study was to evaluate the relationship between prostate cancer risk and the presence of single nucleotide polymorphisms (SNPs) in the genes involved in HRR, that is,RAD51(rs1801320 and rs1801321),RAD51B(rs10483813 and rs3784099),XRCC2(rs3218536), andXRCC3(rs861539). Polymorphisms were analyzed by PCR-RFLP and Real-Time PCR in 101 patients with prostate adenocarcinoma and 216 age- and sex-matched controls. A significant relationship was detected between theRAD51gene rs1801320 polymorphism and increased prostate cancer risk. Our results indicate that theRAD51gene rs1801320 polymorphism may contribute to prostate cancer susceptibility in Poland.

The prostate cancer risk locus at 10q11 is associated with DNA repair capacity

DNA Repair ◽  
2012 ◽  
Vol 11 (8) ◽  
pp. 693-701 ◽  
Author(s):  
Antje E. Rinckleb ◽  
Harald M. Surowy ◽  
Manuel Luedeke ◽  
Dominic Varga ◽  
Mark Schrader ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Repair ◽  
Cancer Risk ◽  
Prostate Cancer Risk ◽  
Repair Capacity ◽  
Dna Repair Capacity ◽  
Risk Locus

scholarly journals Bad neighbours: hypoxia and genomic instability in prostate cancer

2020 ◽  
Vol 93 (1115) ◽  
pp. 20200087 ◽  
Author(s):  
Jack Ashton ◽  
Robert Bristow
Keyword(s):  
Prostate Cancer ◽  
Dna Repair ◽  
Genomic Instability ◽  
Tumour Progression ◽  
Clonal Evolution ◽  
Treatment Strategies ◽  
Repair Capacity ◽  
Functional Studies ◽  
Dna Repair Capacity ◽  
Mechanistic Basis

Prostate cancer (PCa) is a clinically heterogeneous disease and has poor patient outcome when tumours progress to castration-resistant and metastatic states. Understanding the mechanistic basis for transition to late stage aggressive disease is vital for both assigning patient risk status in the localised setting and also identifying novel treatment strategies to prevent progression. Subregions of intratumoral hypoxia are found in all solid tumours and are associated with many biologic drivers of tumour progression. Crucially, more recent findings show the co-presence of hypoxia and genomic instability can confer a uniquely adverse prognosis in localised PCa patients. In-depth informatic and functional studies suggests a role for hypoxia in co-operating with oncogenic drivers (e.g. loss of PTEN) and suppressing DNA repair capacity to alter clonal evolution due to an aggressive mutator phenotype. More specifically, hypoxic suppression of homologous recombination represents a “contextual lethal“ vulnerability in hypoxic prostate tumours which could extend the application of existing DNA repair targeting agents such as poly-ADP ribose polymerase inhibitors. Further investigation is now required to assess this relationship on the background of existing genomic alterations relevant to PCa, and also characterise the role of hypoxia in driving early metastatic spread. On this basis, PCa patients with hypoxic tumours can be better stratified into risk categories and treated with appropriate therapies to prevent progression.

High-Throughput Screening Platform for Nanoparticle-Mediated Alterations of DNA Repair Capacity

ACS Nano ◽  
2021 ◽  
Author(s):  
Sneh M. Toprani ◽  
Dimitrios Bitounis ◽  
Qiansheng Huang ◽  
Nathalia Oliveira ◽  
Kee Woei Ng ◽  
...  
Keyword(s):  
Dna Repair ◽  
High Throughput ◽  
High Throughput Screening ◽  
Repair Capacity ◽  
Dna Repair Capacity ◽  
Screening Platform

scholarly journals DNA Repair Gene Polymorphism and the Risk of Mitral Chordae Tendineae Rupture

2015 ◽  
Vol 2015 ◽  
pp. 1-6
Author(s):  
Aysel Kalayci Yigin ◽  
Mehmet Bulent Vatan ◽  
Ramazan Akdemir ◽  
Muhammed Necati Murat Aksoy ◽  
Mehmet Akif Cakar ◽  
...  
Keyword(s):  
Dna Repair ◽  
Fragment Length Polymorphism ◽  
Control Group ◽  
Chordae Tendineae ◽  
Repair Gene ◽  
Repair Capacity ◽  
Dna Repair Capacity ◽  
Dna Repair Gene ◽  
Increased Risk ◽  
Polymerase Chain

Polymorphisms in Lys939Gln XPC gene may diminish DNA repair capacity, eventually increasing the risk of carcinogenesis. The aim of the present study was to evaluate the significance of polymorphism Lys939Gln in XPC gene in patients with mitral chordae tendinea rupture (MCTR). Twenty-one patients with MCTR and thirty-seven age and sex matched controls were enrolled in the study. Genotyping of XPC gene Lys939Gln polymorphism was carried out using polymerase chain reaction- (PCR-) restriction fragment length polymorphism (RFLP). The frequencies of the heterozygote genotype (Lys/Gln-AC) and homozygote genotype (Gln/Gln-CC) were significantly different in MCTR as compared to control group, respectively (52.4% versus 43.2%,p=0.049; 38.15% versus 16.2%,p=0.018). Homozygote variant (Gln/Gln) genotype was significantly associated with increased risk of MCTR (OR = 2.059; 95% CI: 1.097–3.863;p=0.018). Heterozygote variant (Lys/Gln) genotype was also highly significantly associated with increased risk of MCTR (OR = 1.489; 95% CI: 1.041–2.129;p=0.049). The variant allele C was found to be significantly associated with MCTR (OR = 1.481; 95% CI: 1.101–1.992;p=0.011). This study has demonstrated the association of XPC gene Lys939Gln polymorphism with MCTR, which is significantly associated with increased risk of MCTR.

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