OBJECTIVETo test the association between XRCC1 gene polymorphisms and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families through a family-based association study.

METHODSA total of 2134 study subjects from 457 Cantonese nuclear families were recruited in the study. Each family had two parents and at least one offspring with nasopharyngeal carcinoma. Genotyping for three single nucleotide polymorphisms in XRCC1 gene, including rs1799782 (C > T), rs25489 (G > A) and rs25487 (G > A), were performed with PCR-RFLP assay. The genotype data were analyzed with family-based association test (FBAT) software to check linkage and association between the three genetic markers and susceptibility of nasopharyngeal carcinoma.

RESULTSFBAT analysis showed XRCC1 gene genotypes and haplotypes were not significantly associated with nasopharyngeal carcinoma in our study population (rs1799782: chi(2) = 1.006, P = 0.605; rs25489: chi(2) = 0.470, P = 0.790; rs25487: chi(2) = 2.563, P = 0.278; haplotype: chi(2) = 3.004, P = 0.557, global statistic). For rs25487, the G allele (major allele) showed increased transmission under dominant model (Z = 1.985, P = 0.047). Whereas the C allele (minor allele) exhibited reduced transmission under recessive model (Z = -1.985, P = 0.047). However, no increased/reduced transmission was observed under additive model and with global statistic.

CONCLUSIONThere is no evidence of an association between polymorphisms in XRCC1 gene and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families is observed in this study.

DNA Damage ; DNA Repair ; DNA-Binding Proteins ; genetics ; Gene Frequency ; Genotype ; Humans ; Nasopharyngeal Neoplasms ; genetics ; Pedigree ; Polymorphism, Single Nucleotide ; Surveys and Questionnaires ; X-ray Repair Cross Complementing Protein 1

OBJECTIVEThe aim of this study was to evaluate the effects of XRCCl gene polymorphisms and its haplotype on the susceptibility of pancreatic carcinoma.

METHODSPeripheral blood DNA was extracted from 210 pancreatic carcinoma patients and 213 control subjects. SNaPshot technique was used for genotyping seven SNP sites of the XRCCl gene (rs3213403, rs25487, rs1799782, rs731420, rs1001581, rs12611088, and rs3213282). Logistic regression model was performed to analyze the relationship of different genotypes or haplotype and the susceptibility of pancreatic carcinoma.

RESULTSThe frequency for allele A at site rs25487 in the case group was significantly higher than that in the control group (P < 0.05). The frequency of GG, GA and AA genotype between the case group and control group had statistically significant differences (P < 0.05). Compared with GG genotype, the risk of pancreatic carcinoma in the subjects carrying mutated allele A (GA+AA) was increased by 0.648 times (P < 0.05). Among them the pancreatic carcinoma risk of individuals carrying A allele was increased by 0.552 times compared with the individuals carrying G allele. The frequency of allele and genotype at site rs1799782 in the case group and control group had a significant difference (P < 0.05). Compared with the CC genotype, the risk of pancreatic carcinoma in the subjects carrying mutated allele T (CT+TT) was increased by 0.683 times. Among them the pancreatic carcinoma risk of individuals carrying T allele was increased by 0.549 times compared with the individuals carrying C allele. Significant differences were observed in linkage disequilibrium between any two of the seven SNPs (P < 0.05), the frequency of H4-AGCCCGC, H6-GGCCCGG or H7-AGCCTAG haplotypes was significantly lower in the case group than that in the control group (P < 0.05).

CONCLUSIONSThe single nucleotide polymorphisms of rs25487 and rs1799782 for XRCC1 gene may be correlated with the occurrence of pancreatic carcinoma. The haplotypes of H4-AGCCCGC, H6-GGCCCGG and H7-AGCCTAG might be a potential genetic protective factor for the occurrence of pancreatic carcinoma.

Alleles ; DNA-Binding Proteins ; genetics ; metabolism ; Genetic Predisposition to Disease ; epidemiology ; Genotype ; Haplotypes ; Humans ; Pancreatic Neoplasms ; epidemiology ; Polymorphism, Single Nucleotide ; X-Rays ; X-ray Repair Cross Complementing Protein 1

OBJECTIVETo study the mechanism of the apoptosis induced by N-[4-hydroxyphenyl] retinamide (4-HPR) in bladder cancer cell line T24, and the involvement of DNA damage and repair.

METHODST24 cells were treated with 4-HPR at the concentration of 2.5, 5.0 and 10.0 micromol/L, and the cell grow inhibition was measured by cell counting assay. The fluorescent intensity of reactive oxygen species (ROS) was determined by spectrofluorometer. The apoptosis was measured by flow cytometry and DNA fragment assay. The expression of XRCC1 protein and activation of caspase-3 were detected by Western blot.

RESULTS4-HPR induced apoptosis in T24 cell. A dose-dependent increase in the percentage of apoptosis cells was observed (1.8%, 4.0% and 10.5% respectively at 2.5, 5.0, 10.0 micromol/L 4HPR). In the meantime, ROS level in the cell was increased (peaked at 3 fold). It also caused down-regulation of the expression of XRCC1, and activation of caspase-3. Vitamin C effectively inhibited ROS rise induced by 4-HPR, and also partially inhibited cell growth, apoptosis, and down-regulation of the expression of XRCC1.

CONCLUSIONThe generation of ROS and DNA damage may be the major mechanism of the apoptosis of bladder cancer cell line T24 induced by 4-HPR.

Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; DNA Damage ; DNA Repair ; DNA-Binding Proteins ; metabolism ; Fenretinide ; pharmacology ; Humans ; Reactive Oxygen Species ; metabolism ; Urinary Bladder Neoplasms ; metabolism ; pathology ; X-ray Repair Cross Complementing Protein 1

OBJECTIVETo study the association of polymorphisms in the X-ray repair cross-complementing gene 1 (XRCC1) and papillary thyroid carcinoma (PTC).

METHODSA hospital based, matched case-control study was carried out. The polymorphisms in XRCC1 for 105 pairs of cases with PTC and controls were identified by PCR-RFLP.

RESULTSThe frequencies of Arg/Arg, Arg/Trp and Trp/Trp genotypes at XRCC1 Arg194Trp site were 47.6%, 49.5% and 2.9% among cases compared to 45.7%, 48.6% and 5.7% among controls. There was no statistically significant difference between the two groups (chi(2) = 1.07, P = 0.59). The frequencies of Arg/Arg, Arg/Gln and Gln/Gln genotypes at XRCC1 Arg399Gln site were 46.7%, 41.9% and 11.4% among cases, while 54.2%, 42.9% and 2.9% among controls respectively. There was statistically significant difference between the two groups (chi(2) = 6.40, P = 0.04). Individuals with Gln/Gln genotype had a 3.65-fold increased risk of developing PTC compared to Arg/Arg genotype (OR = 4.65, 95% CI: 1.24 - 17.45). The multivariate conditional logistic regression analysis showed that the XRCC1 Arg399Gln polymorphism, negative life events and X-irradiation history were associated with PTC, with odds ratios of 2.71 (95% CI: 1.22 - 6.05), 5.34 (95% CI: 1.40 - 20.38) and 0.38 (95% CI: 0.12 - 0.72) respectively. However, XRCC1 Arg194Trp polymorphism, drinking tea, fruit and economic levels did not show statistically significant associations with PTC.

CONCLUSIONThe Gln/Gln genotype at XRCC1 Arg399Gln site and negative life events significantly increased while X-irradiation history decreased the risk of developing PTC.

Adult ; Carcinoma, Papillary ; etiology ; genetics ; Case-Control Studies ; DNA Repair ; genetics ; DNA, Neoplasm ; genetics ; DNA-Binding Proteins ; genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Thyroid Neoplasms ; etiology ; genetics ; X-ray Repair Cross Complementing Protein 1

OBJECTIVETo explore the relationship between polymorphisms of DNA repair gene XRCC1 and susceptibility to radiation injury.

METHODSIn 1:1 case-control study, 113 abnormal chromosome workers exposed to ionizing radiation were selected as cases and 113 normal chromosome as controls who matched with case for sex, age (+/- 5 years), nation, type of work, the same or more but in 2 years work length and the same similar levels of the cumulative exposure radiation dose. Genotypes were analysed using PCR based restriction fragment length polymorphism techniques.

RESULTSThe frequency of XRCC1 26304TT allele in case group (18.58%) was significantly higher than that in control group (7.08%), with OR for radiation damage being 3.47 (95% CI 1.43 - 8.44, P < 0.05). No association was observed between XRCC1 G27466A and G28152A and susceptibility to radiation injury.

CONCLUSIONThe mutation of XRCC1 C26304T is related with the susceptibility to radiation injury. The polymorphisms of XRCC1 G27466A and G28152A are not found to have association with abnormal chromosomes.

Adult ; Case-Control Studies ; Chromosome Aberrations ; DNA Repair ; DNA-Binding Proteins ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Radiation Injuries ; genetics ; X-ray Repair Cross Complementing Protein 1

The purpose of this study was to explore the association between X-ray repair cross-complementing group 1 (XRCC1)gene polymorphism and non-Hodgkin's lymphoma risk. A total of 282 non-Hodgkin's lymphoma (NHL) patients and 231 normal controls were used to investigate the effect of three XRCC1 gene polymorphisms (rs25487, rs25489, rs1799782) on susceptibility to non-Hodgkin's lymphoma. Genotyping was performed by using SNaPshot method. All statistical analyses were done with R software. Genotype and allele frequencies of XRCC1 were compared between the patients and controls by using the chi-square test. Crude and adjusted odd ratios and 95% confidence intervals were calculated by using logistic regression on the basis of genetic different models. For four kinds of NHL, subgroup analyses were also conducted. Combined genotype analyses of the three XRCC1 polymorphisms were also done by using logistic regression. The results showed that the variant genotype frequency was not significantly different between the controls and NHL or NHL subtype cases. Combined genotype analyses of XRCC1 399-280-194 results showed that the combined genotype was not associated with risk of NHL overall, but the VT-WT-WT combined genotype was associated with the decreased risk of T-NHL (OR: 0.21; 95%CI (0.06-0.8); P = 0.022), and the WT-VT-WT combined genotype was associated with the increased risk of FL(OR:15.23; 95%CI (1.69-137.39); P = 0.015). It is concluded that any studied polymorphism (rs25487, rs25489, rs1799782) alone was not shown to be rela-ted with the risk of NHL or each histologic subtype of NHL. The combined genotype with mutation of three SNP of XRCC1 was not related to the risk of NHL. However, further large-scale studies would be needed to confirm the association of decreased or increased risk for T-NHL and FL with the risk 3 combined SNP mutants of XRCC1 polymorphism.
Case-Control Studies ; China ; epidemiology ; DNA Repair ; DNA-Binding Proteins ; genetics ; Female ; Humans ; Lymphoma, Non-Hodgkin ; epidemiology ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Risk Factors ; X-ray Repair Cross Complementing Protein 1

OBJECTIVE: To study genetic polymorphism of XRCC1 Arg399Gln and the laryngeal cancer risk. METHOD: A case-control study was performed on 60 patients with laryngeal squamous cell carcinoma and 120 random healthy control group. The two groups were matched by sex and age. Multiplex SNaPshot technic was used to explore polymorphism of DNA repair gene XRCC1 Arg399Gln in distribution of patient with laryngeal squamous cell carcinoma and normal control. RESULT: The frequency of XRCC1c. 399Arg/Gln+Gln/Gln genotypes in the case group was higher than that in the control group (P < 0.05). The expression of the three nations (chinese, uyhur, kazak) was Respectively a 1.47, 1.32, 0.77 fold increased risk of laryngeal cancer for individuals arrying XRCC1c. 399Arg/Gln+Gln/Gln genotypes (OR = 1.47, 95% CI = 0.46-4.69), compared with subjects carryin Arg/Arg genotype. CONCLUSION The polymorphism of XRCC1Arg399GIn might be associated with the susceptibility of laryngeal cancer. The mutation of XRCC1c. 399 Arg-->Gln might lead to a increased risk of laryngeal cancer.
Aged ; Case-Control Studies ; China ; epidemiology ; DNA Repair ; DNA-Binding Proteins ; genetics ; Ethnic Groups ; genetics ; Female ; Humans ; Laryngeal Neoplasms ; epidemiology ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; X-ray Repair Cross Complementing Protein 1

OBJECTIVETo investigate the regulatory effect and significance of transcription factor E2F1 on X-ray repair cross2 complementing 1 (XRCC1).

METHODSSaos2 cells were transfected with the E2F1 expression vectors (tet-E2F1) and mutated E2F1 expression vectors (tet-132E). XRCC1 promotor luciferase reporter vector was constructed and transfected into Saos2 cells together with E2F1, E2F2, E2F3 and E2F4 expression vectors at different amount. The cells were collected 36 hours post-transfection for luciferase assays and absorbance was read at 570 nm.

RESULTSCotransfection of increasing amounts of E2F1 expression vector with the XRCC1 promoter-luciferase reporter caused a dose-dependent increase in luciferase activation. In contrast, DNA binding incompetent E2F1 (132E) could not activate the XRCC1 promoter-luciferase reporter.

CONCLUSIONE2F1 could upregulate endogenous XRCC1 expression and stimulate the XRCC1 promoter.

Cell Line, Tumor ; DNA-Binding Proteins ; genetics ; metabolism ; E2F1 Transcription Factor ; genetics ; metabolism ; Gene Expression ; Genes, Reporter ; Humans ; Promoter Regions, Genetic ; Protein Binding ; Up-Regulation ; X-ray Repair Cross Complementing Protein 1

OBJECTIVETo evaluate the association between the polymorphisms of X-ray repair cross complementing group 1 (XRCC1) and human 8-oxoguanine glycosylase I (hOGG1) gene and the risk for laryngeal carcinoma.

METHODSThis is a case-control study comprised of two groups: 72 patients with laryngeal squamous carcinoma, and 72 controls without laryngeal carcinoma. The PCR-restriction fragment length polymorphism method was used to analyze the XRCC1-Arg399Gln, hOGG1-Ser326Cys polymorphisms.

RESULTSThe frequencies of XRCC1-399Arg/Gln+ Gln/Gln and hOGG1-326Ser/Cys+ Cys/Cys genotypes in the case group were higher than that of the control group(P< 0.05). There was a 3.37-fold or 2.54-fold increased risk of laryngeal carcinoma for individuals carrying XRCC1-399Arg/Gln+ Gln/Gln or hOGG1-326Ser/Cys+ Cys/Cys genotypes, compared with subjects carrying XRCC1-Arg/Arg or hOGG1-Ser/Ser genotype, respectively. No statistically significant differences were found between the smoking group and non-smoking group for risk of laryngeal carcinoma.

CONCLUSIONThe amino acid replacement of XRCC1-399Arg to Gln and hOGG1-326Ser to Cys might lead to an increased risk of laryngeal carcinoma. The study demonstrated the positive association between the polymorphisms of XRCC1 and hOGG1 genes and laryngeal carcinoma.

Aged ; Carcinoma ; genetics ; DNA Glycosylases ; genetics ; DNA-Binding Proteins ; genetics ; Female ; Genetic Predisposition to Disease ; genetics ; Humans ; Laryngeal Neoplasms ; genetics ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics ; X-ray Repair Cross Complementing Protein 1

OBJECTIVETo investigate the correlation of single nucleotide polymorphisms (SNP) of XRCC1 gene to hereditary susceptibility of colorectal cancer.

METHODSXRCC1 genotypes in 124 colorectal cancer patients and 214 matched healthy people as control were analyzed by SnaP Shot SNP-typing technique. Five different inheritance models including codominant, dominant, recessive, overdominant and log-additive were analyzed using logistic regression model. The haplotype distribution was estimated with phase and its correlation with the risk of colorectal cancer was evaluated.

RESULTSThe frequencies of mutant 25487G-A, 25489C-T and 1799782C-T alleles were 0.20, 0.11, 0.32 respectively in the patients, and 0.23, 0.13, 0.34 in the controls. There was no significant correlation of polymophisms of XRCC1 gene to the risk of colorectal cancer in 5 different inheritance models (P>0.05). GCT, GCC, ACC and GTC were the most common haplotypes and the odds ratios were 1, 1.35, 0.90 and 0.84 respectively. There was no significant difference of distribution between 2 groups in haplotypes.

CONCLUSIONPolymorphisms of XRCC1 gene, including rs25487, rs25489, rs1799782, are not associated with to the risk of colorectal cancer.

Colorectal Neoplasms ; genetics ; DNA-Binding Proteins ; genetics ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Logistic Models ; Male ; Middle Aged ; Models, Genetic ; Polymorphism, Single Nucleotide ; X-ray Repair Cross Complementing Protein 1