scholarly journals Polymorphism of DNA repair genes XRCC1 280, XRCC1 194, XRCC1 339 and XPD 751 with stomach cancer

2011 ◽  
Vol 10 (6) ◽  
pp. 35-39
Author(s):  
S. S. Rakitin ◽  
A. I. Dmitriyeva ◽  
V. V. Novitsky ◽  
I. A. Kuznetsova ◽  
B. A. Avkhimenko
Keyword(s):  
Gastric Cancer ◽  
Dna Repair ◽  
Excision Repair ◽  
Molecular Genetic ◽  
Dna Repair Genes ◽  
Repair Gene ◽  
Relative Risks ◽  
Polymorphic Variants ◽  
Gastric Cancer Patients ◽  
Repair Genes

We evaluated the frequency distribution of polymorphic variants in DNA repair genes XRCC1 280, XRCC1 194, XRCC1 399 and XPD 751 gastric cancer patients and healthy controls, leading to new fundamental knowledge and molecular genetic markers of gastric cancer. Statistically significant differences were identified in the two groups for the three excision repair gene XRCC1 280, XRCC1 399 and XPD 751, relative risks were calculated of gastric cancer in carriers of the minor variants of these genes.

scholarly journals DNA Repair Gene XRCC1 and XPD Polymorphisms and Gastric Cancer Risk: A Case-Control Study Outcome from Kashmir, India

2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Bushra Nissar ◽  
Showkat A. Kadla ◽  
Nuzhat Shaheen Khan ◽  
Idrees A. Shah ◽  
Misbah Majid ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Dna Repair ◽  
Dna Repair Genes ◽  
Gastric Cancer Risk ◽  
Repair Gene ◽  
Xrcc1 Arg399gln ◽  
Dna Repair Gene ◽  
Kashmiri Population ◽  
Polymorphic Variants ◽  
Repair Genes

Coding polymorphisms in several DNA repair genes have been reported to affect the DNA repair capacity and are associated with genetic susceptibility to many human cancers, including gastric cancer. An understanding of these DNA repair gene polymorphisms might assess not only the risk of humans exposed to environmental carcinogens but also their responses to different therapeutical approaches, which target the DNA repair pathway. In the present study, polymorphic variants of two DNA repair genes, XRCC1 Arg399Gln and XPD Lys751Gln, were chosen to be studied in association with gastric cancer susceptibility in the Kashmiri population. A total of 180 confirmed cases of gastric cancer (GC) and 200 hospital-based controls from Government Shri Maharaja Hari Singh Hospital, Srinagar, were included in the study. The genotyping for XRCC1 and XPD genes was carried out by polymerase chain reaction-restriction fragment length polymorphism. We found that tobacco smoking is strongly associated with GC risk (OR = 25.65; 95% CI: 5.49–119.7). However, we did not find any association of polymorphism of XRCC1 Arg399Gln (OR = 1.56; 95% CI: 0.32–7.82) and XPD Lys751Gln (OR = 0.46; CI: 0.10–2.19) with GC risk in the study population. The combination of genotypes and gender stratification of XRCC1 and XPD genotypic frequency did not change the results. Consumption of large volumes of salt tea was also not associated with gastric cancer risk. Polymorphic variants of XRCC1 Arg399Gln and XPD Lys751Gln are not associated with the risk of gastric cancer in the Kashmiri population. However, replicative studies with larger sample size are needed to substantiate the findings.

Prognostic value of DNA repair gene based on stratification of gastric cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 12-12
Author(s):  
Jinjia Chang ◽  
Midie Xu ◽  
Hui Sun ◽  
Wenhua Li ◽  
Min Ye ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Dna Repair ◽  
Clustering Analysis ◽  
Molecular Subtypes ◽  
Expression Profiles ◽  
Dna Repair Genes ◽  
Repair Gene ◽  
Dna Repair Gene ◽  
Key Genes ◽  
Repair Genes

12 Background: DNA repair genes can be used as prognostic biomarkers in many types of cancer. We aimed to identify prognostic DNA repair genes in patients with gastric cancer (GC) by systematically bioinformatic approaches using web-based database. Methods: Global gene expression profiles from altogether 1,325 GC patients’ samples from six independent datasets were included in the study. Clustering analysis was performed to screen potentially abnormal DNA repair genes related to the prognosis of GC, followed by unsupervised clustering analysis to identify molecular subtypes of GC. Characteristics and prognosis differences were analyzed among these molecular subtypes, and modular key genes in molecular subtypes were identified based on changes in expression correlation. Multivariate Cox proportional hazard analysis was used to find the independent prognostic gene. Kaplan-Meier method and log-rank test was used to estimate correlations of key DNA repair genes with GC patients’overall survival. Results: There were 57 key genes significantly associated to GC patients’ prognosis, and patients were stratified into three molecular clusters based on their expression profiles, in which patients in Cluster 3 showed the best survival (P < 0.05). After a three-phase training, test and validation process, the expression profile of 13 independent key DNA repair genes were identified can classify the prognostic risk of patients. Compared with patients with low-risk score, patients with high risk score in the training set had shorter overall survival (P < 0.0001). Furthermore, we verified equivalent findings by these key DNA repair genes in the test set (P < 0.0001) and the independent validation set (P = 0.0024). Conclusions: Our results suggest a great potential for the use of DNA repair gene profiling as a powerful marker in prognostication and inform treatment decisions for GC patients.

Patients with Systemic Sclerosis Present Increased DNA Damage Differentially Associated with DNA Repair Gene Polymorphisms

2014 ◽  
Vol 41 (3) ◽  
pp. 458-465 ◽  
Author(s):  
Gustavo Martelli Palomino ◽  
Carmen L. Bassi ◽  
Isabela J. Wastowski ◽  
Danilo J. Xavier ◽  
Yara M. Lucisano-Valim ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Systemic Sclerosis ◽  
Blood Cells ◽  
Gene Polymorphisms ◽  
Peripheral Blood Cells ◽  
Dna Repair Genes ◽  
Repair Gene ◽  
Dna Repair Gene ◽  
Repair Genes

Objective.Patients with systemic sclerosis (SSc) exhibit increased toxicity when exposed to genotoxic agents. In our study, we evaluated DNA damage and polymorphic sites in 2 DNA repair genes (XRCC1Arg399Gln andXRCC4Ile401Thr) in patients with SSc.Methods.A total of 177 patients were studied for DNA repair gene polymorphisms. Fifty-six of them were also evaluated for DNA damage in peripheral blood cells using the comet assay.Results.Compared to controls, the patients as a whole or stratified into major clinical variants (limited or diffuse skin involvement), irrespective of the underlying treatment schedule, exhibited increased DNA damage.XRCC1(rs: 25487) andXRCC4(rs: 28360135) allele and genotype frequencies observed in patients with SSc were not significantly different from those observed in controls; however, theXRCC1Arg399Gln allele was associated with increased DNA damage only in healthy controls and theXRCC4Ile401Thr allele was associated with increased DNA damage in both patients and controls. Further, theXRCC1Arg399Gln allele was associated with the presence of antinuclear antibody and anticentromere antibody. No association was observed between these DNA repair gene polymorphic sites and clinical features of patients with SSc.Conclusion.These results corroborate the presence of genomic instability in SSc peripheral blood cells, as evaluated by increased DNA damage, and show that polymorphic sites of theXRCC1andXRCC4DNA repair genes may differentially influence DNA damage and the development of autoantibodies.

scholarly journals DNA Repair Gene Expression Adjusted by the PCNA Metagene Predicts Survival in Multiple Cancers

2019 ◽  
Author(s):  
Leif Peterson ◽  
Tatiana Kovyrshina
Keyword(s):  
Gene Expression ◽  
Dna Repair ◽  
Gene Selection ◽  
P Value ◽  
Survival Prediction ◽  
Dna Repair Genes ◽  
Repair Gene ◽  
A Genome ◽  
Dna Repair Gene ◽  
Repair Genes

Removal of the proliferation component of gene expression by PCNA adjustment has been addressed in numerous survival prediction studies for breast cancer and all cancers in the TCGA. These studies indicate that widespread co-regulation of proliferation upwardly biases survival prediction when gene selection is performed on a genome-wide basis. In addition, removal of the correlative effects of proliferation does not reduce the random bias associated with survival prediction using random gene selection. Since most cancers become addicted to DNA repair as a result of forced cellular replication, increased oxidation, and repair deficiencies from oncogenic loss or genetic polymorphisms, we pursued an investigation to remove the proliferation component of expression in DNA repair genes to determine survival prediction. This translational hypothesis-driven focus on DNA repair genes is directly amenable to finding new sets of DNA repair genes that could potentially be studied for inhibition therapy. Overall survival (OS) prediction was evaluated in 18 cancers by using normalized RNA-Seq data for 126 DNA repair genes with expression available in TCGA. Transformations for normality and adjustments for age at diagnosis, stage, and PCNA metagene expression were performed for all DNA repair genes. We also analyzed genomic event rates (GER) for somatic mutations, deletions, and amplification in driver genes and DNA repair genes. After performing empirical p-value testing with use of randomly selected gene sets, it was observed that OS could be predicted significantly by sets of DNA repair genes for 61% (11/18) of the cancers. Interestingly, PARP1 was not a significant predictor of survival for any of the 11 cancers. Results from cluster analysis of GERs indicates that the most opportunistic cancers for inhibition therapy may be AML, colorectal, and renal papillary, because of potentially less confounding due to lower GERs for mutations, deletions, and amplifications in DNA repair genes. However, the most opportunistic cancer for inhibition therapy is likely to be AML, since it showed the lowest GERs for mutations, deletions, and amplifications in DNA repair genes. In conclusion, our hypothesis-driven focus to target DNA repair gene expression adjusted for the PCNA metagene as a means of predicting OS in various cancers resulted in statistically significant sets of genes.

scholarly journals TAp63γ enhances nucleotide excision repair through transcriptional regulation of DNA repair genes

DNA Repair ◽  
2012 ◽  
Vol 11 (2) ◽  
pp. 167-176 ◽  
Author(s):  
Juan Liu ◽  
Meihua Lin ◽  
Cen Zhang ◽  
Duoduo Wang ◽  
Zhaohui Feng ◽  
...  
Keyword(s):  
Dna Repair ◽  
Transcriptional Regulation ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Dna Repair Genes ◽  
Nucleotide Excision ◽  
Repair Genes

scholarly journals DNA Repair Gene Expression Adjusted by the PCNA Metagene Predicts Survival in Multiple Cancers

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 501 ◽  
Author(s):  
Leif Peterson ◽  
Tatiana Kovyrshina
Keyword(s):  
Gene Expression ◽  
Dna Repair ◽  
Statistical Significance ◽  
Candidate Gene Approach ◽  
Dna Repair Genes ◽  
Repair Gene ◽  
Genome Wide ◽  
A Genome ◽  
Dna Repair Gene ◽  
Repair Genes

Removal of the proliferation component of gene expression by proliferating cell nuclearantigen (PCNA) adjustment via statistical methods has been addressed in numerous survivalprediction studies for breast cancer and all cancers in the Cancer Genome Atlas (TCGA). Thesestudies indicate that the removal of proliferation in gene expression by PCNA adjustment removesthe statistical significance for predicting overall survival (OS) when gene selection is performed ona genome-wide basis. Since cancers become addicted to DNA repair as a result of forced cellularreplication, increased oxidation, and repair deficiencies from oncogenic loss or geneticpolymorphisms, we hypothesized that PCNA adjustment of DNA repair gene expression does notremove statistical significance for OS prediction. The rationale and importance of this translationalhypothesis is that new lists of repair genes which are predictive of OS can be identified to establishnew targets for inhibition therapy. A candidate gene approach was employed using TCGARNA-Seq data for 121 DNA repair genes in 8 molecular pathways to predict OS for 18 cancers.Statistical randomization test results indicate that after PCNA adjustment, OS could be predictedsignificantly by sets of DNA repair genes for 61% (11/18) of the cancers. These findings suggest thatremoval of the proliferation signal in expression by PCNA adjustment does not remove statisticalsignificance for predicting OS. In conclusion, it is likely that previous studies on PCNA adjustmentand survival were biased because genes identified through a genome-wide approach are stronglyco-regulated by proliferation.

scholarly journals Evidence that DNA repair genes, a family of tumor suppressor genes, are associated with evolution rate and size of genomes

2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Konstantinos Voskarides ◽  
Harsh Dweep ◽  
Charalambos Chrysostomou
Keyword(s):  
Dna Repair ◽  
Pathway Analysis ◽  
Adaptive Radiation ◽  
Evolutionary Rate ◽  
Excision Repair ◽  
Special Role ◽  
Dna Repair Genes ◽  
Vertebrate Species ◽  
Repair Genes ◽  
Evolutionary Stasis

AbstractAdaptive radiation and evolutionary stasis are characterized by very different evolution rates. The main aim of this study was to investigate if any genes have a special role to a high or low evolution rate. The availability of animal genomes permitted comparison of gene content of genomes of 24 vertebrate species that evolved through adaptive radiation (representing high evolutionary rate) and of 20 vertebrate species that are considered as living fossils (representing a slow evolutionary rate or evolutionary stasis). Mammals, birds, reptiles, and bony fishes were included in the analysis. Pathway analysis was performed for genes found to be specific in adaptive radiation or evolutionary stasis respectively. Pathway analysis revealed that DNA repair and cellular response to DNA damage are important (false discovery rate = 8.35 × 10−5; 7.15 × 10−6, respectively) for species evolved through adaptive radiation. This was confirmed by further genetic in silico analysis (p = 5.30 × 10−3). Nucleotide excision repair and base excision repair were the most significant pathways. Additionally, the number of DNA repair genes was found to be linearly related to the genome size and the protein number (proteome) of the 44 animals analyzed (p < 1.00 × 10−4), this being compatible with Drake’s rule. This is the first study where radiated and living fossil species have been genetically compared. Evidence has been found that cancer-related genes have a special role in radiated species. Linear association of the number of DNA repair genes with the species genome size has also been revealed. These comparative genetics results can support the idea of punctuated equilibrium evolution.

Homologous recombination deficiency (HRD) in patients with pancreatic cancer (PC) and response to chemotherapy.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 317-317 ◽  
Author(s):  
Safi Shahda ◽  
Kirsten Timms ◽  
Ashley Ibrahim ◽  
Julia E. Reid ◽  
Harvey M Cramer ◽  
...  
Keyword(s):  
Dna Repair ◽  
Homologous Recombination ◽  
Locally Advanced ◽  
Response To Therapy ◽  
Dna Repair Genes ◽  
Repair Gene ◽  
Dna Repair Gene ◽  
Response To Chemotherapy ◽  
Mutation Data ◽  
Repair Genes

317 Background: Mutations or copy number abnormalities of genes involved in homologous recombination occur in PC. DNA-based measures of HRD have been developed and may help identify tumors with better response to DNA damaging agents. This study aimed to describe the mutation and HRD status of PC and determine their association with treatment response and outcome. Methods: This was a retrospective analysis of tumor samples from patients treated at Indiana University for locally advanced or metastatic PC. Patients were included if they received gemcitabine/nab-paclitaxel or FOLFIRINOX and had adequate follow up to assess survival and response to therapy. Tumor analysis generated a 3-biomarker (LOH, TAI, LST) HRD score and mutation data for 45 genes. Results: Ninety-one samples met inclusion criteria, 78 (15 FFPE and 63 FNA) generated mutation data. HRD analysis was successful for 57; the primary cause of failure low tumor %. The final analysis set consisted of 78 samples with mutation status, including 57 with HRD scores (range= 5 -61 (median=18,)). Six BRCA1/ 2 mutations were detected, 5 had high HRD scores, with 4 in the top decile (p=0.011). Other DNA repair gene mutations ( ATM=3, ATR=1, BRIP1=1 and FANCI=1) were detected, but most retained one functional allele and were not associated with HRD score. There was no statistically significant correlation between HRD score and response to FOLFIRINOX (OR per interquartile range = 1.40, p=0.32 adjusted for treatment). HRD score was not associated with PFS or OS. For FOLFIRINOX, median survival times for low vs. high HRD (dichotomized at the median) were 5.3 vs. 9.4 months PFS (p=0.049) and OS 12.3 vs. 11.3 months (p=0.89). For gemcitabine/nab-paclitaxel, mPFS was 6.1 vs. 4.6 months (p=0.88), and mOS was 14.4 vs. 11.4 months (p=0.29). Conclusions: Mutations in DNA repair genes occur in PC, and HRD scores can be generated in the majority of cases. HRD score was not significantly associated with higher response rate or prolonged survival in relation to FOLFIRINOX in this small non-randomized retrospective cohort. Larger studies to examine the association of mutations in DNA repair genes and HRD may be needed to detect significant associations.

A Polymorphism Study on Detoxification and DNA Repair Genes in 700 MDS Patients Demonstrates An Association Between Genotype and An Aberrant Karyotype

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2690-2690
Author(s):  
C. Seedhouse ◽  
Stephanie Fischer ◽  
Christina Ganster ◽  
Christa Fonatsch ◽  
Peter Valent ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Genetic Stability ◽  
Genetic Instability ◽  
Dna Repair Genes ◽  
Repair Gene ◽  
Dna Repair Gene ◽  
Increased Risk ◽  
Xrcc3 Thr241met ◽  
Repair Genes

Abstract The maintenance of genetic stability within haematopoietic stem cells is essential for normal haematopoiesis and this is emphasised by the association of leukemias and myelodysplastic syndromes (MDS) with genetic instability. DNA is normally protected from damage via a number of complex pathways including detoxification and DNA repair pathways. Inefficient processing of DNA damage may result in an increased susceptibility to leukemia and MDS. Genetic polymorphisms exist in many genes within the DNA damage processing pathways, some of which affect the cells ability to maintain genetic stability. We have studied polymorphisms in the homologous DNA repair genes RAD51 (RAD51-g135c) and XRCC3 (XRCC3-Thr241Met) and the detoxification gene GSTM1 (deletion polymorphism) in more 700 MDS samples. The GSTM1 polymorphism was studied using PCR, and the RAD51 and XRCC3 genotypes were assayed simultaneously using a SNaPshot technique. The genotype distributions of RAD51-g135c and GSTM1 did not differ significantly from those reported in the literature. However the distribution of the XRCC3-Thr241Met polymorphism was found to be significantly different, with an over-representation of the variant Met allele, when compared to previously published frequencies in control populations1 (odds ratio (OR) 1.8; 95% confidence interval (CI) 1.3–2.6, p&lt;0.001). Whilst the presence of a single polymorphic variant may display only a subtle effect, polymorphic variants of more than one gene involved in the same pathway are likely to be biologically important with respect to the cellular ability to maintain genetic integrity and hence may play a role in MDS pathogenesis. RAD51, XRCC3 and GSTM1 genotypes were therefore studied in combined analyses. Similar to studies in AML1, the double DNA repair gene variant (RAD51–135c/XRCC3–241) was over-represented in MDS compared to a control population (OR 3.8; 95% CI 1.6–9.3, p=0.002). The triple variant genotype (RAD51–135c/XRCC3–241Met/GSTM1-null) was associated with a further increased risk of MDS (OR 13.5; 95% CI 1.8–102.8, p=0.01). More detailed analysis was undertaken to compare the polymorphic distributions in MDS with aberrant karyotypes. When the single genes were assessed, the GSTM1 null genotype was the only one to be over-represented in MDS with an aberrant karyotype compared to MDS with a normal karyotype (OR 1.6; 95% CI 1.05–2.5). Interestingly, when analysing the genotypes with respect to the XRCC3/RAD51 combined genotypes the presence of homozygous wild type alleles of one DNA repair gene matched with the presence of a variant allele of the other DNA repair gene is significantly protective against karyotypic abnormalities when compared to the double WT patients (OR 0.29; 95% CI 0.29–0.78; p=0.003). Collectively these results suggest that polymorphisms in genes which process DNA damage play a significant role in MDS pathogenesis and may also contribute to genetic instability in MDS.

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