Gastric Cardia Carcinoma is Associated with the Promoter -77T>C Gene Polymorphism of X-Ray Cross-Complementing Group 1 (XRCC1) (original) (raw)
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Journal of Gastrointestinal Surgery, 2009
Purpose X-ray repair cross complementing group 1 (XRCC1) is one of the major DNA repair proteins involved in the basexcision repair pathway. Several single-nucleotide polymorphisms in the XRCC1 gene are identified and related with increased cancer risk development. In particular, the -77T>C polymorphism located on the promoter region relates with lung cancer risk development. The aim of this study is to analyze the -77T>C allelic frequencies in a population composed of 456 primary gastric cancer patients (GC) and 507 blood donor controls. Methods GC patients were observed at the University of Siena, Italy; clinicopathological data and family history were available for the cancer group. The control group is composed of blood donors. Constitutional genomic DNA was PCR amplified, and XRCC1 -77T>C was detected using restriction enzyme BsrB I and analyzed in a 3% agarose gel. Results The -77C>C homozygous genotype was significantly associated with increased risk of gastric cardia carcinoma (p=0.023) with an odds ratio of 1.65 (95% confidence interval 1.14 to 2.4). In the family history stratification, we report a significant association (p=0.043) between the -77T>C polymorphism and GC cases with familial lung cancer aggregation. Conclusions Our results suggest that the XRCC1 -77T>C polymorphism is a relevant host susceptibility factor for gastric cardia cancer development and specific subsets of familial clustering of GC.
Genetic polymorphisms of XRCC1 and risk of gastric cancer
Cancer Letters, 2002
Coding polymorphisms of the DNA repair gene XRCC1 have been shown to affect the DNA repair capacity and to be associated with genetic susceptibility to carcinogenesis. In our association study between three amino acid substitution polymorphisms of XRCC1 (Arg194Trp, Arg280His, and Arg399Gln) and the risk of gastric cancer in the Korean population, none of the polymorphisms were associated with increased risk of gastric cancer. We then extended our study by building haplotypes of the entire XRCC1 gene with six single neuclotide polymorphisms (SNPs), including two novel polymorphisms at the 5 0flanking sequence. When haplotype frequencies in cases and controls and haplotype-specific odds ratios (ORs) were estimated, haplotype A (194Trp, 280Arg, and 399Arg) was associated with significant reduction in gastric cancer risk (adjusted OR ¼ 0.65, 95% CI ¼ 0.43-0.99) whereas haplotype D (194Arg, 280Arg, and 399Arg alleles) was a risk type for gastric cancer (adjusted OR ¼ 1.57, 95% CI ¼ 0.93-2.65). The association with the haplotype D was more pronounced in the cancers of antrum (adjusted OR ¼ 2.06, 95% CI ¼ 1.03-2.00). Our results suggest that the haplotype estimation is advantageous for association studies of such a complex disease as gastric cancer.
Research in Molecular Medicine, 2020
Background: Gastric cancer is one of the most common malignancies in the world. It may result from a defect in the genes involved in DNA repair. One of the essential genes in the repair pathway is the XRCC1 gene that its polymorphisms in the human population play a role in gastric cancer susceptibility. The main purpose of this study was to investigate the association of 194C/T and 399G/A polymorphisms of the XRCC1 gene with gastric cancer in an Iranian population. Materials and Methods: A total of 66 patients with gastric cancer and 67 control individuals were enrolled in our study. Following DNA extraction from blood samples, polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Results: The allele frequencies of C/T of XRCC1-194C/T in the control and patients groups were 83.17% and 71.29%, respectively. Moreover, The allele frequencies of G/A of XRCC1-399G/A in control and patient groups were 66.34% and 62.38%, respectively. Our results indicated a significant positive association between the distribution T/C alleles and the risk of gastric cancer (χ 2 : 5.37 and P=0.02), but no significant association was found in the distribution G/A alleles (χ 2 : 0.47 and P=0.48). Conclusion: Altogether, these findings indicate a positive association between the distribution of 194T/C alleles of XRCC1 and the risk of gastric cancer and the presence of the C allele may increase the risk of gastric cancer.
American Journal of Epidemiology, 2011
The authors performed a systematic review and meta-analysis of associations of the x-ray repair crosscomplementing 1 gene (XRCC1) single nucleotide polymorphisms (SNPs) Arg194Trp, Arg280His, and Arg399Gln with gastric cancer risk, based on eligible studies retrieved from electronic databases for the period January 2000-December 2009. Ultimately, 12, 6, and 3 studies were found to be eligible for meta-analyses of Arg399Gln, Arg194Trp, and Arg280His, respectively. Regrouping was adopted in accordance with the most probably appropriate genetic models. Potential sources of heterogeneity were sought out. For overall gastric cancer, the pooled odds ratios for Arg399Gln, Arg194Trp, and Arg280His were 1.04 (95% confidence interval (CI): 0.90, 1.20; P ¼ 0.572), 0.83 (95% CI: 0.68, 1.01; P ¼ 0.059), and 1.18 (95% CI: 0.92, 1.50; P ¼ 0.194), respectively. After stratification of the Arg399Gln SNP data by anatomic type (cardia vs. noncardia), the pooled odds ratio was 1.07 (95% CI: 0.84, 1.37; P ¼ 0.568). The authors conclude that the 3 SNPs evaluated are not associated with risk of gastric cancer. The Arg399Gln SNP is not associated with the cardia type of gastric cancer. Evidently, the heterogeneity regarding the Arg399Gln SNP across studies is not explained by ethnicity, genotyping technique, sample size, or date of publication.
Polymorphisms in DNA repair genes XRCC2 and XRCC3 risk of gastric cancer in Turkey
We studied the prevalence of polymorphisms in genes XRCC2 and XRCC3 in stomach cancer patients who lived in North Eastern Turkey. A total of 61 cancer patients and 78 controls were included in this study. Single nucleotide changes were studied in XRCC2 and XRCC3 genes at locus Arg188His and Th r241Met. Blood samples were taken from the patients and controls, and DNA was isolated. Th e regions of interest were amplifi ed using a polymerase chain reaction method. After amplifi cation, we used restriction enzymes (HphI and NcoI) to digest the amplifi ed product. Digested product was then run through gel electrophoresis. We identifi ed changes in the nucleotides in these specifi c regions. It was found that the Arg188His polymorphism of the XRCC2 gene was about 39 (24 out of the 61) among cancer patients. However, only 15 (12 out of 78) of the control group indicated this polymorphism. We also observed that 18 of the 61 cancer patients (29) carried the Th r241Met polymorphism of the XRCC3 gene whereas 11 of the 78 (14) individuals in the control group had the polymorphism. Our results showed a signifi cant diff erence in polymorphism ratios between the cancer patients and health control group for the regions of interest. Th is result clearly showed that these polymorphisms increase the risk of stomach cancer and might be a strong marker for early diagnosis of gastric cancer.
British Journal of Cancer Research, 2018
Objectives: Cancer is a genetic disease characterized by an imbalance between cell growth and regulatory factors. The genes XRCC1 and XRCC3 encode a protein that contributes to the integrity of the genome. Our study was aimed at evaluating XRCC1 Arg399Gln and XRCC3 Thr241Met polymorphisms in a sample of gastric cancer patients in the city of Macapá, Amapá, Brazil. Methodology: We analyzed 160 DNA samples (60 patients and 100 control samples). DNA samples were amplified and analyzed by PCR-RFLP with the restriction enzymes MspI and NlaIII. Results: the molecular analysis revealed that 41,6% and 63,8% of the patients samples had the Arg399Gln and Thr241Met genotypes. Conclusion: Our findings revealed that most samples of gastric cancer patients analyzed exhibited XRCC1 Arg399Gln and XRCC3 Thr241Met polymorphisms. Our goal is to apply these and future results to assist in the treatment of patients, since exposure to environmental factors as well as genetic alterations in other genes, acting alone or interacting with each other, may increase the risk of developing gastric cancer.
BMC cancer, 2017
Previous studies have found that polymorphisms of the DNA repair gene X-ray repair cross-complementing group 1(XRCC1) and environmental factors are both associated with an increased risk of stomach cancer, but no study has reported on the potential additive effect of these factors among Thai people. The aim of this study was to investigate whether the risk of stomach cancer from XRCC1 gene polymorphisms was modified by environmental factors in the Thai population. Hospital-based matched case-control study data were collected from 101 new stomach cancer cases and 202 controls, which were recruited from2002 to 2006 and were matched for gender and age. Genotype analysis was performed using real-time PCR-HRM. The data were analysed by the chi-square test and conditional logistic regression. The Arg/Arg homozygote polymorphism of the XRCC1 gene was associated with an increased risk of stomach cancer in the Thai population (OR adj, 3.7; 95%CI, 1.30-10.72) compared with Gln/Gln homozygosit...
XRCC3 Thr241Met polymorphism and gastric cancer susceptibility: a meta-analysis
Clinics and research in hepatology and gastroenterology, 2014
X-ray repair cross-complementing group 3 (XRCC3) is responsible for maintaining the integrity of the genome, playing a critical role in protecting it against mutations which lead to cancer. Polymorphisms at exons 7 of the XRCC3 gene may alter the XRCC3 repair efficiency. The aim of this study is to derive a precise estimation of the relationship between XRCC3 Thr241Met polymorphism and gastric cancer (GC) risk. Two investigators independently searched the databases of Pubmed, EMBASE and China National Knowledge Infrastructure (CNKI) up to May 15, 2013. Odds ratio (OR) and 95% confidence intervals (CI) for XRCC3 Thr241Met polymorphism and GC were calculated in a fixed- or random- effects model depending on statistical heterogeneity. This meta-analysis included 9 case-control studies, which included 2209 cases and 3269 controls. Overall, the combined results based on all studies indicated that there was no association between XRCC3 Thr241Met polymorphism and GC susceptibility for all ...
Asian Pacific journal of cancer prevention : APJCP, 2016
The XRCC1 protein facilitates various DNA repair pathways; single-nucleotide polymorphisms (SNPs) in this gene are associated with a risk of gastrointestinal cancer (GIC) with inconsistent results, but no data have been previously reported for the Sabah, North Borneo, population. We accordingly investigated the XRCC1 Arg194Trp and Arg399Gln SNPs in terms of GIC risk in Sabah. We performed genotyping for both SNPs for 250 GIC patients and 572 healthy volunteers using a polymerase chain reaction- restriction fragment length polymorphism approach. We validated heterozygosity and homozygosity for both SNPs using direct sequencing. The presence of a variant 194Trp allele in the Arg194Trp SNP was significantly associated with a higher risk of GIC, especially with gastric and colorectal cancers. We additionally found that the variant 399Gln allele in Arg399Gln SNP was associated with a greater risk of developing gastric cancer. Our combined analysis revealed that inheritance of variant all...
2018
Risk of Gastric Cancer in the Amazon Region –Brazil Artemis Socorro do N. Rodrigues*1, Gabriel Espíndola1, Tainá Vanzeler1, Lorrayne Lacerda1, Suzane Cabral1, Olavo Picanco Jr1 1 Laboratory of Molecular Biology of the Federal University of Amapá-UNIFAP, Biological Sciences Course Macapá, Amapá, Brazil Corresponding author: Dr. Artemis Socorro do Nascimento Rodrigues, Laboratory of Molecular Biology of the Federal University of Amapá-UNIFAP, Biological Sciences Course Macapá, Amapá, Brazil, Tel: 559633121767; E-mail: artemis@unifap.br