The Experts below are selected from a list of 3210 Experts worldwide ranked by ideXlab platform
Cecilia Arici - One of the best experts on this subject based on the ideXlab platform.
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Bladder cancer, GSTs, NAT1, NAT2, SULT1A1, XRCC1, XRCC3, XPD genetic polymorphisms and coffee consumption: a case–control study
European Journal of Epidemiology, 2008Co-Authors: Loredana Covolo, Donatella Placidi, Umberto Gelatti, Angela Carta, Antonio Scotto Di Carlo, Paolo Lodetti, Antonio Piccichè, Grazia Orizio, Marcello Campagna, Cecilia AriciAbstract:The aim of the study was to investigate NAT1, NAT2, GSTM1, GSTT1, GSTP1, SULT1A1, XRCC1, XRCC3 and XPD genetic polymorphisms, coffee consumption and risk of bladder cancer (BC) through a hospital-based case–control study. The study population included 197 incident BC cases and 211 controls. The association between genetic polymorphisms, coffee drinking and BC risk was assessed by logistic regression taking into account age, education, tobacco smoking and occupational exposures to polycyclic aromatic hydrocarbons and aromatic amines. No association was found between the genetic polymorphisms investigated and BC risk according to coffee consumption apart of a significant increased BC risk among GSTP1 105-114 Val carriers heavy coffee drinkers (>3 cups/day) (OR 3.18, 95%CI 1.06–9.55). In conclusion our findings suggest a very limited role, if any, of genetic polymorphisms investigated in modulating the BC risk in coffee drinkers.
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bladder cancer gsts nat1 nat2 sult1a1 xrcc1 XRCC3 xpd genetic polymorphisms and coffee consumption a case control study
European Journal of Epidemiology, 2008Co-Authors: Loredana Covolo, Donatella Placidi, Umberto Gelatti, Angela Carta, Paolo Lodetti, Antonio Piccichè, Grazia Orizio, Marcello Campagna, Antonio Scotto Di Carlo, Cecilia AriciAbstract:The aim of the study was to investigate NAT1, NAT2, GSTM1, GSTT1, GSTP1, SULT1A1, XRCC1, XRCC3 and XPD genetic polymorphisms, coffee consumption and risk of bladder cancer (BC) through a hospital-based case–control study. The study population included 197 incident BC cases and 211 controls. The association between genetic polymorphisms, coffee drinking and BC risk was assessed by logistic regression taking into account age, education, tobacco smoking and occupational exposures to polycyclic aromatic hydrocarbons and aromatic amines. No association was found between the genetic polymorphisms investigated and BC risk according to coffee consumption apart of a significant increased BC risk among GSTP1 105-114 Val carriers heavy coffee drinkers (>3 cups/day) (OR 3.18, 95%CI 1.06–9.55). In conclusion our findings suggest a very limited role, if any, of genetic polymorphisms investigated in modulating the BC risk in coffee drinkers.
Ulla Vogel - One of the best experts on this subject based on the ideXlab platform.
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polymorphisms of the xrcc1 XRCC3 and xpd genes and risk of colorectal adenoma and carcinoma in a norwegian cohort a case control study
BMC Cancer, 2006Co-Authors: Camilla Furu Skjelbred, Ingerlise Hansteen, Mona Saebo, Hakan Wallin, Bjorn A Nexo, Per Christian Hagen, Inger Marie Bowitz Lothe, Steinar Aase, Egil Johnson, Ulla VogelAbstract:Background Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of developing cancer. For colorectal cancer the importance of mutations in mismatch repair genes has been extensively documented. Less is known about other DNA repair pathways in colorectal carcinogenesis. In this study we have focused on the XRCC1, XRCC3 and XPD genes, involved in base excision repair, homologous recombinational repair and nucleotide excision repair, respectively.
Camilla Furu Skjelbred - One of the best experts on this subject based on the ideXlab platform.
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influence of dna repair gene polymorphisms of hogg1 xrcc1 XRCC3 ercc2 and the folate metabolism gene mthfr on chromosomal aberration frequencies
Mutation Research, 2006Co-Authors: Camilla Furu Skjelbred, Marit Svendsen, Vera Haugan, Kjell Oskar Clausen, Martin Veel Svendsen, Ingerlise HansteenAbstract:Abstract We have studied the effect of genetic polymorphisms in the DNA repair genes hOGG1 , XRCC1 , XRCC3 , ERCC2 and the MTHFR gene in the folate metabolism on the frequencies of cells with chromosomal aberrations (CA), chromosome-type aberrations (CSA), chromatid-type aberrations (CTA), chromatid breaks (CTB) and chromatid gaps (CTG) scored in peripheral blood lymphocytes from 651 Norwegian subjects of Caucasian descendant. DNA was extracted from fixed cell suspensions. The log-linear Poisson regression model was used for the combined data which included age, smoking, occupational exposure and genotype for 449 subjects. Our results suggest that individuals carrying the hOGG1 326Cys or the XRCC1 399Gln allele have an increased risk of chromosomal damage, while individuals carrying the XRCC1 194Trp or the ERCC2 751Gln allele have a reduced risk regardless of smoking habits and age. Individuals carrying the XRCC1 280His allele had an increased risk of CSA which was only apparent in non-smokers. This was independent of age. A protective effect of the XRCC3 241Met allele was only found in the older age group in non-smokers for CA, CSA and CTA, and in smokers for CSA. In the youngest age group, the opposite effect was found, with an increased risk for CA, CTA and CTG in smokers. Carrying the MTHFR 222Val allele gave an increased risk for chromosome and chromatid-type aberrations for both non-smokers and smokers, especially for individuals in the older age group, and with variable results in the youngest age group. The variables included in the different regression models accounted, however, for only 4–10% of the variation. The frequency ratio for CTG was significantly higher than for CTA and CTB for only 7 of the 43 comparisons performed. Some of the gap frequencies diverge from the trend in the CA, CSA, CTA and CTB results.
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polymorphisms of the xrcc1 XRCC3 and xpd genes and risk of colorectal adenoma and carcinoma in a norwegian cohort a case control study
BMC Cancer, 2006Co-Authors: Camilla Furu Skjelbred, Ingerlise Hansteen, Mona Saebo, Hakan Wallin, Bjorn A Nexo, Per Christian Hagen, Inger Marie Bowitz Lothe, Steinar Aase, Egil Johnson, Ulla VogelAbstract:Background Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of developing cancer. For colorectal cancer the importance of mutations in mismatch repair genes has been extensively documented. Less is known about other DNA repair pathways in colorectal carcinogenesis. In this study we have focused on the XRCC1, XRCC3 and XPD genes, involved in base excision repair, homologous recombinational repair and nucleotide excision repair, respectively.
Fung Chang Sung - One of the best experts on this subject based on the ideXlab platform.
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polymorphisms of the xrcc1 XRCC3 xpd genes and colorectal cancer risk a case control study in taiwan
BMC Cancer, 2005Co-Authors: Fung Chang Sung, Reiping Tang, Chung Rong Changchieh, Lingling HsiehAbstract:Recent studies relating to the association between DNA repair-gene polymorphisms and colorectal cancer risk would, to the best of our knowledge, appear to be very limited. This study was designed to examine the polymorphisms associated with three DNA repair genes, namely: XRCC1 Arg399Gln, XRCC3 Thr241Met and XPD Lys751Gln, and investigate their role as susceptibility markers for colorectal cancer. We conducted a case-control study including 727 cases of cancer and 736 hospital-based age- and sex-matched healthy controls to examine the role of genetic polymorphisms of three DNA-repair genes (XRCC1, XRCC3 and XPD) in the context of colorectal cancer risk for the Taiwanese population. Genomic DNA isolated from 10 ml whole blood was used to genotype XRCC1 Arg399Gln, XRCC3 Thr241Met and XPD Lys751Gln by means of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. The risk for colorectal cancer did not appear to differ significantly amongst individuals featuring the XRCC1 399Arg/Arg genotype (OR = 1.18; 95% CI, 0.96–1.45), the XRCC3 241Thr/Thr genotype (OR = 1.25; 95% CI, 0.88–1.79) or the XPD 751Gln allele (OR = 1.20; 95% CI, 0.90–1.61), although individuals featuring a greater number of risk genotypes (genotype with OR greater than 1) did experience a higher risk for colorectal cancer when compared to those who didn't feature any risk genotypes (Trend test P = 0.03). Compared with those individuals who didn't express any putative risk genotypes, individuals featuring all of the putative risk genotypes did experience a significantly greater cancer risk (OR = 2.43, 95% CI = 1.21–4.90), particularly for individuals suffering tumors located in the rectum (OR = 3.18, 95% CI = 1.29–7.82) and diagnosed prior to the age of 60 years (OR = 4.90, 95% CI = 1.72–14.0). Our results suggest that DNA-repair pathways may simultaneously modulate the risk of colorectal cancer for the Taiwanese population, and, particularly for rectal cancer and younger patients.
L. H. Thompson - One of the best experts on this subject based on the ideXlab platform.
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tetratricopeptide motif mediated interaction of fancg with recombination proteins XRCC3 and brca2
DNA Repair, 2006Co-Authors: Shobbir Hussain, L. H. Thompson, James B Wilson, Eric Blom, Patrick Sung, Susan M Gordon, Gary M Kupfer, Hans Joenje, Christopher G Mathew, Nigel J JonesAbstract:Abstract Fanconi anaemia is an inherited chromosomal instability disorder characterised by cellular sensitivity to DNA interstrand crosslinkers, bone-marrow failure and a high risk of cancer. Eleven FA genes have been identified, one of which, FANCD1 , is the breast cancer susceptibility gene BRCA2 . At least eight FA proteins form a nuclear core complex required for monoubiquitination of FANCD2. The BRCA2/FANCD1 protein is connected to the FA pathway by interactions with the FANCG and FANCD2 proteins, both of which co-localise with the RAD51 recombinase, which is regulated by BRCA2. These connections raise the question of whether any of the FANC proteins of the core complex might also participate in other complexes involved in homologous recombination repair. We therefore tested known FA proteins for direct interaction with RAD51 and its paralogs XRCC2 and XRCC3. FANCG was found to interact with XRCC3, and this interaction was disrupted by the FA-G patient derived mutation L71P. FANCG was co-immunoprecipitated with both XRCC3 and BRCA2 from extracts of human and hamster cells. The FANCG–XRCC3 and FANCG–BRCA2 interactions did not require the presence of other FA proteins from the core complex, suggesting that FANCG also participates in a DNA repair complex that is downstream and independent of FANCD2 monoubiquitination. Additionally, XRCC3 and BRCA2 proteins co-precipitate in both human and hamster cells and this interaction requires FANCG. The FANCG protein contains multiple tetratricopeptide repeat motifs (TPRs), which function as scaffolds to mediate protein–protein interactions. Mutation of one or more of these motifs disrupted all of the known interactions of FANCG. We propose that FANCG, in addition to stabilising the FA core complex, may have a role in building multiprotein complexes that facilitate homologous recombination repair.
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XRCC3 atpase activity is required for normal XRCC3 rad51c complex dynamics and homologous recombination
Journal of Biological Chemistry, 2004Co-Authors: Nazumi Alice Yamada, John M. Hinz, Vicki L Kopf, Kathryn D Segalle, L. H. ThompsonAbstract:Abstract Homologous recombinational repair preserves chromosomal integrity by removing double-strand breaks, cross-links, and other DNA damage. In eukaryotic cells, the Rad51 paralogs (XRCC2/3, Rad51B/C/D) are involved in this process, although their exact functions are largely undetermined. All five paralogs contain ATPase motifs, and XRCC3 exists in a single complex with Rad51C. To examine the function of this Rad51C-XRCC3 complex, we generated mammalian expression vectors that produce human wild-type XRCC3 or mutant XRCC3 with either a nonconservative mutation (K113A) or a conservative mutation (K113R) in the GKT Walker A box of the ATPase motif. The three vectors were independently transfected into XRCC3-deficient irs1SF Chinese hamster ovary cells. Wild-type XRCC3 complemented irs1SF cells, albeit to varying degrees, whereas ATPase mutants had no complementing activity, even when the mutant protein was expressed at comparable levels to that in wild-type-complemented clones. Because of dysfunction of the mutants, we propose that ATP binding and hydrolyzing activities of XRCC3 are essential. We tested in vitro complex formation by wild-type and mutant XRCC3 with His6-tagged Rad51C upon co-expression in bacteria, nickel-affinity purification, and Western blotting. Wild-type and K113A mutant XRCC3 formed stable complexes with Rad51C and co-purified with Rad51C, whereas the K113R mutant did not and was predominantly insoluble. The addition of 5 mm ATP but not ADP also abolished complex formation by the wild-type proteins. These results suggest that XRCC3 probably regulates the dissociation and formation of Rad51C-XRCC3 complex through ATP binding and hydrolysis with both processes being essential for the ability of the complex to participate in homologous recombinational repair.
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interactions involving the rad51 paralogs rad51c and XRCC3 in human cells
Nucleic Acids Research, 2002Co-Authors: Claudia Wiese, L. H. Thompson, David W Collins, Joanna S Albala, Amy Kronenberg, David SchildAbstract:Homologous recombinational repair of DNA double-strand breaks and crosslinks in human cells is likely to require Rad51 and the five Rad51 paralogs (XRCC2, XRCC3, Rad51B/Rad51L1, Rad51C/Rad51L2 and Rad51D/Rad51L3), as has been shown in chicken and rodent cells. Previously, we reported on the interactions among these proteins using baculovirus and two- and three-hybrid yeast systems. To test for interactions involving XRCC3 and Rad51C, stable human cell lines have been isolated that express (His)6-tagged versions of XRCC3 or Rad51C. Ni2+-binding experiments demonstrate that XRCC3 and Rad51C interact in human cells. In addition, we find that Rad51C, but not XRCC3, interacts directly or indirectly with Rad51B, Rad51D and XRCC2. These results argue that there are at least two complexes of Rad51 paralogs in human cells (Rad51C–XRCC3 and Rad51B–Rad51C–Rad51D–XRCC2), both containing Rad51C. Moreover, Rad51 is not found in these complexes. X-ray treatment did not alter either the level of any Rad51 paralog or the observed interactions between paralogs. However, the endogenous level of Rad51C is moderately elevated in the XRCC3-overexpressing cell line, suggesting that dimerization between these proteins might help stabilize Rad51C.
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Rare microsatellite polymorphisms in the DNA repair genesXRCC1, XRCC3 andXRCC5 associated with cancer in patients of varying radiosensitivity
Somatic Cell and Molecular Genetics, 1997Co-Authors: E. A. Price, S. L. Bourne, R. Radbourne, P. A. Lawton, J. Lamerdin, L. H. Thompson, J. E. ArrandAbstract:DNA repair defects might contribute both to cancer progression and to the extreme reactions to radiotherapy observed in ≈5% of patients. Polymorphic microsatellites in three DNA repair genes, XRCC1, XRCC3 and XRCC5, were analyzed for possible linkage to cancer status or clinical radiosensitivity. XRCC1, 3 and 5 proteins are involved in single-strand DNA break rejoining, recombinational repair, and double-strand DNA break rejoining respectively. Mendelianly inherited microsatellite polymorphisms in these genes were analyzed in three groups: volunteers with no cancer history; radiosensitive cancer patients; cancer patients with acceptable reactions to radiotherapy. Rare heterozygous alterations in all three gene regions were found solely in the cancer subpopulation. Association testing between these rare polymorphisms and cancer status revealed a significant association for XRCC1 (P=0.005), and XRCC3 (P=0.004). There was also an association between these polymorphisms and clinical radiosensitivity for XRCC1 (P=0.03), and XRCC3 (P=0.005).
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rare microsatellite polymorphisms in the dna repair genes xrcc1 XRCC3 and xrcc5 associated with cancer in patients of varying radiosensitivity
Somatic Cell and Molecular Genetics, 1997Co-Authors: E. A. Price, S. L. Bourne, R. Radbourne, P. A. Lawton, J. Lamerdin, L. H. Thompson, J. E. ArrandAbstract:DNA repair defects might contribute both to cancer progression and to the extreme reactions to radiotherapy observed in ≈5% of patients. Polymorphic microsatellites in three DNA repair genes, XRCC1, XRCC3 and XRCC5, were analyzed for possible linkage to cancer status or clinical radiosensitivity. XRCC1, 3 and 5 proteins are involved in single-strand DNA break rejoining, recombinational repair, and double-strand DNA break rejoining respectively. Mendelianly inherited microsatellite polymorphisms in these genes were analyzed in three groups: volunteers with no cancer history; radiosensitive cancer patients; cancer patients with acceptable reactions to radiotherapy. Rare heterozygous alterations in all three gene regions were found solely in the cancer subpopulation. Association testing between these rare polymorphisms and cancer status revealed a significant association for XRCC1 (P=0.005), and XRCC3 (P=0.004). There was also an association between these polymorphisms and clinical radiosensitivity for XRCC1 (P=0.03), and XRCC3 (P=0.005).
