Influence of Arg399Gln, Arg280His and Arg194Trp XRCC1 gene polymorphisms of Base Excision Repair pathway on the level of 8-oxo-guanine and risk of head and neck cancer in the Polish population

2021 ◽  
pp. 1-10
Author(s):  
Jacek Kabzinski ◽  
Monika Maczynska ◽  
Dariusz Kaczmarczyk ◽  
Ireneusz Majsterek
Keyword(s):  
Dna Repair ◽  
Excision Repair ◽  
Mean Value ◽  
Control Group ◽  
Xrcc1 Gene ◽  
Repair Gene ◽  
Dna Repair Gene ◽  
Increased Risk ◽  
High Level ◽  
Risk Of Cancer

BACKGROUND: Reduced efficiency of DNA repair systems has long been a suspected factor in increasing the risk of cancer. OBJECTIVE: In this work we investigate influence of three selected polymorphisms of DNA repair gene XRCC1 and level of oxidative damage (measured as level of 8-oxo-guanine) on modulation of the risk of HNSCC. METHODS: In group of 359 patients with HNSCC (diagnosed with OSCC) the occurrence of polymorphic variants in Arg399Gln, Arg280His and Arg194Trp of XRCC1 were studied with TaqMan technique. In addition we determined level of 8-oxo-guanine with ELISA. RESULTS: Arg399Gln polymorphism and Arg194Trp polymorphism of XRCC1 gene increases the risk of HNSCC. The coexistence of Arg399Gln and Arg194Trp simultaneously enhances this effect. At the same time, their coexistence with His280His raises the risk to a level higher than in the absence of such coexistence, although the His280His itself is not associated with an increased risk of HNSCC. Patients have higher levels of 8-oxo-guanine than control group, and His280His is polymorphism with highest mean value of 8-oxoG level among studied. CONCLUSION: Patients with HNSCC not only have an increased level of 8-oxoguanine and the Arg399Gln and Arg/Trp of XRCC1 modulate risk of cancer, but there is also a relationship between these two phenomena, and it can be explained using intragenic combinations revealing that a high level of 8-oxoG could be a potential mechanism behind the modulation of HNSCC risk by the polymorphisms studied.

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.

scholarly journals DNA Repair Gene Polymorphisms and Susceptibility to Urothelial Carcinoma in a Southeastern European Population

2021 ◽  
Vol 28 (3) ◽  
pp. 1879-1885
Author(s):  
Maria Samara ◽  
Maria Papathanassiou ◽  
Lampros Mitrakas ◽  
George Koukoulis ◽  
Panagiotis J. Vlachostergios ◽  
...  
Keyword(s):  
Dna Repair ◽  
Urothelial Carcinoma ◽  
European Population ◽  
Nucleotide Polymorphisms ◽  
Environmental Carcinogens ◽  
Repair Gene ◽  
High Exposure ◽  
Dna Repair Gene ◽  
Increased Risk ◽  
Xrcc3 Thr241met

Single nucleotide polymorphisms (SNPs) in DNA repair genes may predispose to urothelial carcinoma of the bladder (UCB). This study focused on three specific SNPs in a population with high exposure to environmental carcinogens including tobacco and alcohol. A case-control study design was used to assess for presence of XPC PAT +/−, XRCC3 Thr241Met, and ERCC2 Lys751Gln DNA repair gene SNPs in peripheral blood from patients with UCB and healthy individuals. One hundred patients and equal number of healthy subjects were enrolled. The XPC PAT +/+ genotype was associated with a 2-fold increased risk of UCB (OR = 2.16; 95%CI: 1.14–4; p = 0.01). The −/+ and +/+ XPC PAT genotypes were more frequently present in patients with multiple versus single tumors (p = 0.01). No association was detected between ERCC2 Lys751Gln genotypes/alleles, and risk for developing UCB. Presence of the XRCC3 TT genotype (OR = 0.14; 95%CI:0.07–0.25; p < 0.01) and of the T allele overall (OR = 0.26; 95%CI:0.16–0.41; p < 0.01) conferred a protective effect against developing UCB. The XPC PAT −/+ and XRCC3 Thr241Met SNPs are associated with predisposition to UCB. The XPC PAT −/+ SNP is also an indicator of bladder tumor multiplicity, which might require a more individualized surveillance and treatment.

scholarly journals Molecular cloning and chromosomal localization of DNA sequences associated with a human DNA repair gene.

1985 ◽  
Vol 5 (2) ◽  
pp. 398-405 ◽  
Author(s):  
J S Rubin ◽  
V R Prideaux ◽  
H F Willard ◽  
A M Dulhanty ◽  
G F Whitmore ◽  
...  
Keyword(s):  
Dna Repair ◽  
Dna Sequences ◽  
Chromosomal Localization ◽  
Excision Repair ◽  
Repair Process ◽  
Human Cells ◽  
Gene Products ◽  
Repair Gene ◽  
Human Dna ◽  
Dna Repair Gene

The genes and gene products involved in the mammalian DNA repair processes have yet to be identified. Toward this end we made use of a number of DNA repair-proficient transformants that were generated after transfection of DNA from repair-proficient human cells into a mutant hamster line that is defective in the initial incision step of the excision repair process. In this report, biochemical evidence is presented that demonstrates that these transformants are repair proficient. In addition, we describe the molecular identification and cloning of unique DNA sequences closely associated with the transfected human DNA repair gene and demonstrate the presence of homologous DNA sequences in human cells and in the repair-proficient DNA transformants. The chromosomal location of these sequences was determined by using a panel of rodent-human somatic cell hybrids. Both unique DNA sequences were found to be on human chromosome 19.

scholarly journals A yeast DNA repair gene partially complements defective excision repair in mammalian cells.

1988 ◽  
Vol 7 (10) ◽  
pp. 3245-3253 ◽  
Author(s):  
C. Lambert ◽  
L. B. Couto ◽  
W. A. Weiss ◽  
R. A. Schultz ◽  
L. H. Thompson ◽  
...  
Keyword(s):  
Dna Repair ◽  
Mammalian Cells ◽  
Excision Repair ◽  
Repair Gene ◽  
Dna Repair Gene

Inheritance of the 194Trp and the 399Gln variant alleles of the DNA repair gene XRCC1 are associated with increased risk of early-onset colorectal carcinoma in Egypt

2000 ◽  
Vol 159 (1) ◽  
pp. 79-86 ◽  
Author(s):  
Sherif Z Abdel-Rahman ◽  
Amr S Soliman ◽  
Melissa L Bondy ◽  
Sherif Omar ◽  
Samy A El-Badawy ◽  
...  
Keyword(s):  
Dna Repair ◽  
Colorectal Carcinoma ◽  
Early Onset ◽  
Repair Gene ◽  
Dna Repair Gene ◽  
Increased Risk ◽  
Variant Alleles

DNA Repair Gene, XRCC1 Polymorphisms Are Associated with Chemotherapy Induced Toxicity in Patients with Diffuse Large B Cell Lymphoma Who Received Frontline R-CHOP Chemotherapy.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1620-1620
Author(s):  
In-Suk Kim ◽  
Gyeong-Won Lee ◽  
Hoon-Gu Kim ◽  
Sun-Young Kong ◽  
HyeonSeok Eom
Keyword(s):  
Dna Repair ◽  
Confidence Interval ◽  
Odds Ratio ◽  
B Cell Lymphoma ◽  
Chop Chemotherapy ◽  
Repair Gene ◽  
Dna Repair Gene ◽  
Increased Risk ◽  
Grade 3 ◽  
Xrcc1 Arg194trp

Abstract BACKGROUND. X-ray repair cross-complementing group I (XRCC1) is a DNA repair gene. Polymorphisms in DNA repair genes may alter protein function and therefore the efficacy of DNA damaging chemotherapy. We retrospectively evaluated the association of three polymorphisms in XRCC1 codon 194 (Arg to Trp), 280 (Arg to His), and 399 (Arg to Gln), with grade 3 or 4 toxicities of primary rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone (R-CHOP) therapy in 145 patients with diffuse large B cell lymphoma (DLBCL). METHODS. A total of 145 patients who received R-CHOP chemotherapy as a frontline regimen DLBCL were included in this retrospective study from 3 hospitals in Korea. The genotypes of XRCC1 at the Arg194Trp, Arg280His, and Arg399Gln were determined by direct sequencing methods. The clinical characteristics, treatment outcomes and grade 3 and 4 toxicities of the patients were compared using Chi-square, Fisher exact, Mann-Whitney U tests, or logistic regression according to the XRCC1 polymorphisms. RESULTS. Carrying at least one variant XRCC1 Arg194Trp alleles (194Arg/Trp or 194Trp/Trp) and XRCC1 Arg399Gln variant alleles (399Arg/Gln or 399Gln/Gln) was associated with a significantly increased risk of grade 3 or 4 gastrointestinal toxicity (Arg194Trp alleles; odds ratio, 3.489; 95% confidence interval, 0.126–1.568; P=0.001, Arg399Gln alleles; odds ratio, 2.577; 95% confidence interval, 0.144–1.096; P=0.011, respectively). The carriers of XRCC1 Arg280His variant alleles (280Arg/His or 280His/His) was associated with grade 3 or 4 neutropenia (odds ratio, 2.047; 95% confidence interval, 0.008–0.450; P=0.043). No differences in the patient characteristics, disease characteristics, response, and survival in patients with DLBCL who received frontline R-CHOP chemotherapy were observed according to three XRCC1 polymorphims. CONCLUSIONS. This study demonstrates that the patients carrying at least one variant XRCC1 Arg194Trp or XRCC1 Arg399Gln alleles have a 2.5-to 3.5-fold increased risk of grade 3 or 4 gastrointestinal toxicity and the patients carrying at least one variant XRCC1 Arg280His allele have a 2.0-fold increased risk of grade 3 or 4 neutropenia when treated with frontline R-CHOP chemotherapy and this has implications for optimizing treatment with such agents.

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.

scholarly journals Repair of UV damage in plants by nucleotide excision repair: Arabidopsis UVH1 DNA repair gene is a homolog of Saccharomyces cerevisiae Rad1

2000 ◽  
Vol 21 (6) ◽  
pp. 519-528 ◽  
Author(s):  
Zongrang Liu ◽  
Gazi Showkat Hossain ◽  
Maria A. Islas-Osuna ◽  
David L. Mitchell ◽  
David W. Mount
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Repair ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Uv Damage ◽  
Repair Gene ◽  
Dna Repair Gene ◽  
Nucleotide Excision

scholarly journals Allele and Genotype Distributions of DNA Repair Gene Polymorphisms in South Indian Healthy Population

2014 ◽  
Vol 6 ◽  
pp. BIC.S19681 ◽  
Author(s):  
Katiboina Srinivasa Rao ◽  
Abialbon Paul ◽  
Annan Sudarsan Arun Kumar ◽  
Gurusamy Umamaheswaran ◽  
Biswajit Dubashi ◽  
...  
Keyword(s):  
Dna Repair ◽  
Xeroderma Pigmentosum ◽  
Excision Repair ◽  
Association Studies ◽  
Healthy Population ◽  
Repair Gene ◽  
South Indian ◽  
Dna Repair Gene ◽  
Genes Encoding ◽  
Hapmap Populations

Various DNA repair pathways protect the structural and chemical integrity of the human genome from environmental and endogenous threats. Polymorphisms of genes encoding the proteins involved in DNA repair have been found to be associated with cancer risk and chemotherapeutic response. In this study, we aim to establish the normative frequencies of DNA repair genes in South Indian healthy population and compare with HapMap populations. Genotyping was done on 128 healthy volunteers from South India, and the allele and genotype distributions were established. The minor allele frequency of Xeroderma pigmentosum group A ( XPA) G23A, Excision repair cross-complementing 2 ( ERCC2)/Xeroderma pigmentosum group D ( XPD) Lys751Gln, Xeroderma pigmentosum group G ( XPG) His46His, XPG Asp1104His, and X-ray repair cross-complementing group 1 ( XRCC1) Arg399Gln polymorphisms were 49.2%, 36.3%, 48.0%, 23.0%, and 34.0% respectively. Ethnic variations were observed in the frequency distribution of these polymorphisms between the South Indians and other HapMap populations. The present work forms the groundwork for cancer association studies and biomarker identification for treatment response and prognosis.

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