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 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 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 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 explore the relationship between the polymorphisms of DNA repair gene (XRCC1 194, 280 and 399) and the chromosomal damage induced by benzene.

METHODSThe chromosomal damage of the peripheral lymphocytes in 459 workers occupationally exposed to benzene and 88 non-exposed controls were detected with cytokinesis-block micronucleus (CBMN) assay. PCR-RFLP technique was used to measure polymorphisms in XRCC1 194, 280 and 399.

RESULTSIt was found that the MN frequency (2.12‰ ± 1.88‰) of the exposed group was significantly higher than that (1.19‰ ± 1.68‰) of the control group (P < 0.05), in the exposed group, the MN frequency (3.00‰ ± 2.76‰) of older workers (> 35 years) was significantly higher than that (2.02‰ ± 1.71‰) of younger workers (≤ 35 years) (P < 0.05). The effect of genetic polymorphisms of XRCC1 on CBMN was not found. The haplotypes AAA/BAA, AAB/AAB, ABA/ABA, ABB/ABB could associated with the increased frequencies of total micronucleus (P < 0.05).

CONCLUSIONBenzene exposure could result in chromosome damage. Age of workers and diplotypes of XRCC1 could associated with chromosomal damage induced by benzene.

Adult ; Benzene ; adverse effects ; DNA Damage ; drug effects ; genetics ; DNA-Binding Proteins ; genetics ; Humans ; Micronuclei, Chromosome-Defective ; Micronucleus Tests ; Occupational Exposure ; Polymorphism, Single Nucleotide ; X-ray Repair Cross Complementing Protein 1 ; Young Adult

AIMTo investigate the association among XRCC1 polymorphisms, smoking, drinking and the risk of prostate cancer (PCa) in men from Han, Southern China.

METHODSIn a case-control study of 207 patients with PCa and 235 cancer-free controls, frequency-matched by age, we genotyped three XRCC1 polymorphisms (codons 194, 280 and 399) using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP) method.

RESULTSAmong the three polymorphisms, we found that the XRCC1 Arg399Gln variant allele was associated with increased PCa risk (adjusted odd ratio [OR]: 1.67, 95% confident interval [CI]: 1.11-2.51), but the XRCC1 Arg194Trp variant allele had a 38% reduction in risk of PCa (adjusted OR: 0.62, 95% CI: 0.41-0.93). However, there was no significant risk of PCa associated with Arg280His polymorphism. When we evaluated the three polymorphisms together, we found that the individuals with 194Arg/Arg wild-type genotype, Arg280His and Arg399Gln variant genotypes had a significantly higher risk of PCa (adjusted OR: 4.31; 95% CI: 1.24-14.99) than those with three wild-type genotypes. In addition, we found that Arg399Gln variant genotypes had a significant risk of PCa among heavy smokers (adjusted OR: 2.04; 95% CI: 1.03-4.05).

CONCLUSIONThese results suggest that polymorphisms of XRCC1 appear to influence the risk of PCa and may modify risks attributable to environmental exposure.

Adenocarcinoma ; blood ; epidemiology ; genetics ; Aged ; China ; epidemiology ; DNA-Binding Proteins ; blood ; genetics ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Odds Ratio ; Polymorphism, Restriction Fragment Length ; Prostatic Neoplasms ; blood ; epidemiology ; genetics ; Risk Factors ; Seroepidemiologic Studies ; X-ray Repair Cross Complementing Protein 1

OBJECTIVETo evaluate the effects of polymorphisms in XRCC1 and APE1 genes on vinyl chloride (VC)-induced chromosomal damage in peripheral lymphocytes.

METHODSIn this study, 317 workers occupationally exposed to VC were recruited from a factory in Shandong Province, China. The micronucleus (MN) frequency in peripheral lymphocytes was used as an indicator of chromosomal damage. Polymerase chain reaction-restriction fragment length polymorphism and created restriction site combined with restriction fragment length polymorphism were used to determine the five single nucleotide polymorphisms in XRCC1 and APE1 genes in the base excision repair pathway. The association of chromosomal damage with these polymorphisms and the haplotype of XRCC1 was analyzed using Poisson regression and PHASE 2.0.2.

RESULTSIt was found that among the VC-exposed workers, individuals with XRCC1 polymorphisms (-77C/T, Arg194Trp, Arg280His, and Arg399Gln) had a significantly higher MN frequency than those with homozygous wild-type genotypes, with frequency ratios (FR) as follows, respectively: FR = 1.21, 95%CI: 1.05∼1.39 (P < 0.05); FR = 1.14, 95%CI: 1.00∼1.38 (P < 0.05); FR = 1.26, 95%CI: 1.11∼1.44 (P < 0.05); FR = 1.23, 95%CI: 1.08∼1.46 (P < 0.05). APE1 Asp148Glu was found of no significant relationship with MN frequency. Haplotype analysis of XRCC1 demonstrated that the MN frequencies in subjects with CTAA/CTAA and CCAA/CTAA were significantly higher than that in those with TCGG/TCGG (FR = 1.19, 95%CI: 1.02∼1.32, P < 0.05; FR = 1.41, 95%CI: 1.02∼1.87, P < 0.05). Furthermore, association was found between accumulated exposure to VC and XRCC1 polymorphisms (-77C/T, Arg194Trp, Arg280His, and Arg399Gln) after adjustment for age, sex, drinking, and smoking.

CONCLUSIONVC can induce chromosomal damage even when the exposure level is lower than the national occupational health standard of China (PC-TWA: 10 mg/m(3)); the polymorphisms in XRCC1 and APE1 are associated with chromosomal damage induced by VC.

Adult ; DNA-(Apurinic or Apyrimidinic Site) Lyase ; genetics ; DNA-Binding Proteins ; genetics ; Female ; Haplotypes ; Humans ; Male ; Micronuclei, Chromosome-Defective ; Middle Aged ; Occupational Exposure ; adverse effects ; Polymorphism, Restriction Fragment Length ; Vinyl Chloride ; poisoning ; X-ray Repair Cross Complementing Protein 1 ; Young Adult