Arg399Gln Single Nucleotide Polymorphisms Research Articles

Association between polymorphisms in the XRCC1 gene and male infertility risk: A meta-analysis.

Background:X-ray repair cross-complementing group 1 (XRCC1) single nucleotide polymorphisms (SNPs) might correlate with male infertility susceptibility. This association has been described; however, the findings remain inconsistent. Consequently, this meta-analysis was conducted to characterize the relationship between XRCC1 SNPs and male infertility susceptibility.Methods/main results:Studies were systematically searched in databases to evaluate the association between SNPs of XRCC1 and infertility in males. The effect measures chosen were the 95% confidence intervals (95% CIs) and odds ratios (ORs). A total of 7 studies, including 6 case-controlled studies on XRCC1 Arg399Gln and 3 case-controlled studies on XRCC1 Arg194Trp, were included. Ultimately, the results of this analysis revealed that XRCC1 Arg399Gln SNPs were significantly associated with infertility in males in homozygote comparisons (GG vs GA+AA: OR = 0.614, 95% CI: 0.40–0.937, P = .024). This meta-analysis did not demonstrate a relationship between XRCC1 Arg194Trp and male infertility risk.Conclusions:Our study indicated that XRCC1 Arg399Gln polymorphism was associated with a significantly decreased male infertility risk, but not XRCC1 Arg194Trp.

Lack of correlation between X-ray repair cross-complementing group 1 gene polymorphisms and the susceptibility to colorectal cancer in a Malaysian cohort.

X-ray repair cross-complementing group 1 (XRCC1) is one of the key components in the base excision repair pathway that repairs erroneous DNA lesions and removes nonbulky base adducts for the maintenance of genome integrity. Studies have revealed that differences in individual DNA repair capacity can impact the interindividual variation in cancer susceptibility, tumour aggressiveness and treatment response. The relationship between XRCC1 and sporadic colorectal cancer (CRC) susceptibility, which is hitherto inconclusive, has been explored in many association studies of different populations. In view of the conflicting findings generated, we aimed to investigate the association between XRCC1 and genetic predisposition to CRC among Malaysians. The present case-control association study was conducted on 130 CRC patients and 212 age-matched healthy controls. The genotyping of XRCC1 Arg194Trp, Arg280His and Arg399Gln single nucleotide polymorphisms was performed with allele-specific real-time PCR approach. This was followed by basic statistical analysis on the single nucleotide polymorphisms and haplotype data obtained. No significant difference in the allele and genotype frequencies was observed between CRC patients and healthy controls (P>0.05). There was also no association observed between XRCC1 haplotypes and CRC (P>0.05). In conclusion, a positive association between XRCC1 gene polymorphisms and CRC risk was not established in our Malaysian population.

Variant Alleles in XRCC1 Arg194Trp and Arg399Gln Polymorphisms Increase Risk of Gastrointestinal Cancer in Sabah, North Borneo.

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 alleles in both SNPs increased the GIC risk in Sabah population. Based on our etiological analysis, we found that subjects ≥50 years and males who carrying the variant 194Trp allele, and Bajau subjects carrying the 399Gln allele had a significantly increased risk of GIC. Our findings suggest that inheritance of variant alleles in XRCC1 Arg194Trp and Arg399Gln SNPs may act as biomarkers for the early detection of GIC, especially for gastric and colorectal cancers in the Sabah population.

The Author Response: Presence of Evolutionary Pressures or Genotyping Error

I would like to thank the interest and comments to our paper entitled polymorphisms and risk of papillary thyroid carcinoma in a Korean sample (1). In our study, we genotyped XRCC1 Arg194Trp and Arg399Gln single nucleotide polymorphisms (SNPs) in 111 papillary thyroid carcinoma patients and 100 normal control subjects. In the results of our study, the XRCC1 Arg194Trp Arg/Trp genotype was significantly associated with a decreased risk of papillary thyroid carcinoma compared to that of Arg/Arg genotype, while the XRCC1 Arg399Gln genotype was not associated with a risk of papillary thyroid carcinoma. I agree with the comments. There was a mistake in the calculation of Hardy-Weinberg equilibrium (HWE). A genotype distribution of XRCC1 Arg194Trp was in HWE (control P = 0.728, case P = 0.768); however, a genotype distribution of XRCC1 Arg399Gln deviated from HWE (control P = 0.0002, case P = 0.0003). The deviation from HWE could be associated with the sampling bias or the presence of evolutionary pressure, and it might be also associated with the genotyping error. As I already mentioned some limitations of our study in the paper, there was a selection bias as a hospital-based case-control study. The control group in our study may not have accurately represented the general population, and the genotype distribution of XRCC1 Arg399Gln deviated from HWE. Also, our study included a relatively small number of cases and controls. Therefore, the results of our study should be interpreted with caution. A further study with using large, matched case-control samples is necessary to validate the genetic effects of XRCC1 polymorphisms in the Korean population.

X-Ray Repair Cross-Complementing Group 1 (XRCC1) Genetic Polymorphisms and Gastric Cancer Risk: A HuGE Review and Meta-Analysis

The authors performed a systematic review and meta-analysis of associations of the x-ray repair cross-complementing 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 = 0.572), 0.83 (95% CI: 0.68, 1.01; P = 0.059), and 1.18 (95% CI: 0.92, 1.50; P = 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 = 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.

XRCC1 Polymorphisms and Risk of Papillary Thyroid Carcinoma in a Korean Sample

Polymorphisms of DNA repair genes, X-ray repair cross-complementing group 1 (XRCC1) might contribute to individual susceptibility to different types of cancers. We analyzed the relationship between XRCC1 polymorphisms and the risk of papillary thyroid carcinoma in a Korean sample. A hospital-based case-control study was performed in 111 papillary thyroid carcinoma patients and 100 normal control subjects. XRCC1 Arg194Trp and Arg399Gln single nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The XRCC1 Arg194Trp Arg/Trp genotype was significantly associated with a decreased risk of papillary thyroid carcinoma compared to that of Arg/Arg genotype (odds ratio [95% confidence intervals]; 0.550 [0.308-0.983]). There was no significant association between XRCC1 Arg399Gln genotypes and risk of papillary thyroid carcinoma. Based on these results, the XRCC1 Arg194Trp Arg/Trp genotype could be used as a useful molecular biomarker to predict genetic susceptibility for papillary thyroid carcinoma in Koreans.

Polymorphisms of XRCC1 gene and risk of gastric cardiac adenocarcinoma

X-ray repair cross complementing 1 (XRCC1) protein plays an important role in base excision repair. Single nucleotide polymorphisms (SNPs) in XRCC1 gene may affect DNA repairing ability and genetic susceptibility to cancer. This study was designed to investigate the correlation of XRCC1 Arg194Trp Arg280His and Arg399Gln SNPs with the risk of gastric cardiac adenocarcinoma (GCA). Genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism assay in 455 patients with GCA and 650 age and sex-matched controls. We did not find any significant difference in allele and genotype distributions of Arg194Trp Arg399Gln between the groups (P > 0.05). However, a significant increase in GCA risk was seen among smokers if they carried at least one XRCC1 280His (Arg280His + His280His) genotype (odds ratio = 1.59, 95%confidence interval = 1.01-2.51) compared with smokers not carrying these genotype. Our results indicated that XRCC1 Arg194Trp and Arg399Gln SNPs might not be associated with the risk of GCA. However, smokers with His allele at codon 280 had a significantly increased risk of GCA.