Ethnicity-stratified analysis of the association between XRCC3 Thr241Met polymorphism and leukemia: an updated meta-analysis.
Ontology highlight
ABSTRACT: Background
Presently, whether X-ray repair cross complementing group 3 (XRCC3) Thr241Met polymorphism is correlated to leukemia risk remains controversial. Because of this reason, the objective of current study is to explore whether XRCC3 Thr241Met polymorphism confers risk to leukemia.Methods
Two independent authors systematically and comprehensively searched Pubmed, Embase, the Cochrane library, Google academic, China National Knowledge Infrastructure (CNKI). Search time is from database foundation to March 2021.Results
Overall, significant associations between leukemia risk and XRCC3 Thr241Met polymorphism were found in Caucasian population by allele contrast (T vs. C: OR 1.20, 95% CI 1.02-1.40), homozygote comparison (TT vs. CC: OR 1.35, 95% CI 1.05-1.73), and recessive genetic model (TT vs. TC/CC: OR 1.31, 95% CI 1.04-1.64).Conclusions
The present meta-analysis suggests that the XRCC3 Thr241Met polymorphism may be a risk factor for leukemia in Caucasian population.
SUBMITTER: Xie Z
PROVIDER: S-EPMC8449464 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:UnlabelledGenetic polymorphism of X-ray repair crosscomplementing group 3 (XRCC3) Thr241Met has been implicated to alter the risk of ovarian cancer, but the results are controversial. In order to get a more precise result, a meta-analysis was performed. All eligible studies were identified through an extensive search in PubMed, Excerpta Medica Database (Embase), Chinese National Knowledge Infrastructure database, and Chinese Biomedical Literature Database before August 2013. The association between the XRCC3 Thr241Met polymorphism and ovarian cancer risk was conducted by odds ratios (ORs) and 95% confidence intervals (95% CIs). Finally, a total of four publications including seven studies with 3,635 cases and 5,473 controls were included in our meta-analysis. Overall, there was no association between XRCC3 Thr241Met polymorphism and risk of ovarian cancer under all five genetic models in overall population (T vs. C: OR = 0.99, 95 % CI = 0.960-1.03, P = 0.752; TT vs. CC: OR = 1.00, 95% CI = 0.91-1.10, P = 0.943; TC vs. TT: OR = 0.97, 95% CI = 0.92-1.04, P = 0.396, Fig. 1; TT vs.Tc/ccOR = 1.00, 95% CI = 0.91-1.12, P = 0.874; TT/TC vs. CC: OR = 0.98, 95% CI = 0.94-1.03, P = 0.486). In the subgroup analysis according to ethnicity, the results suggested that XRCC3 Thr241Met polymorphism was not associated with the risk of ovarian cancer in Caucasians population. No significant association was found between the XRCC3 Thr241 Met polymorphism and the risk of ovarian cancer. Given the limited sample size and ethnicities included in the meta-analysis, further large scaled and well-designed studies are needed to confirm our results.
| S-EPMC3967082 | biostudies-literature
Project description:BackgroundStudies have shown that gene and environmental factors, such as BRCA1/2 mutations, ionized radiation, and chemical carcinogens, are related with breast cancer. X-ray repair cross-complementing group 3 (XRCC3) is involved in homologous repair of double DNA breaks. It was reported that Thr241Met single-nucleotide polymorphism (SNP) in XRCC3 is associated with increased risk of breast cancer. However, the finding remains controversial. The current meta-analysis aims to determine whether XRCC3 Thr241Met polymorphism is associated with increased risk of breast cancer.Material and methodsWe performed a meta-analysis of association between XRCC3 T241M polymorphism and the risk of breast cancer. Crude odds ratios (ORs) together with 95% confidence intervals (CIs) were used to assess the strength of association in dominant, recessive, and homozygote models.ResultsWe included 23 studies consisting of 13513 cases and 14100 controls in our study. For meta-analysis on the entire database, association of the SNP and breast cancer risk was observed in recessive (OR=1.10, 95% CI: 1.03-1.18, p=0.005) and homozygote (OR=1.09, 95% CI: 1.01-1.18, p=0.023) models. For the analysis on the Asian population subgroup, association of the SNP and breast cancer risk was also observed in recessive (OR=1.615, 95% CI: 1.17-2.228, p=0.004) and homozygote (OR=1.609, 95% CI: 1.154-2.241, p=0.005) models. For the evaluation of the patients without family history of breast cancer, association of the SNP and breast cancer risk was observed in dominant (OR=1.364, 95% CI: 1.096-1.698, p=0.005), recessive (OR=1.336, 95% CI: 0.999-1.788, p=0.051) and homozygote (OR=1.492, 95% CI: 1.085-2.051, p=0.014) models.ConclusionsWe can conclude that XRCC3 Thr241Met polymorphism might be associated with breast cancer risk, especially in Asian populations and in patients without family history of breast cancer.
| S-EPMC4627365 | biostudies-literature
Project description:BACKGROUND The X-ray cross-complementing group 3 (XRCC3) gene encodes a protein that plays an important role in homologous recombination repair (HRR) of DNA double-strand break (DSB). Increasing attention has been drawn to the association of XRCC3 T241M polymorphism with various types of human cancers. In this study, a meta-analysis was performed to investigate whether there is an association between XRCC3 T241M polymorphism and thyroid cancer risk. MATERIAL AND METHODS A comprehensive search was conducted and a total of 8 studies that covered 963 thyroid cancer cases and 1942 controls were included in this analysis. The meta-analysis was performed on both overall database and 2 ethnic subgroups (Caucasian and Asian). The fixed-effects model was used to calculate odds ratio (OR) with 95% confidence intervals (CIs). The publication bias was evaluated using Begg's funnel plots and Egger's test. RESULTS A positive association between XRCC3 T241M polymorphism and thyroid cancer risk was found by the analyses of the overall database using both recessive model (OR=1.40, 95% CI=1.08-1.81, P=0.012) and homozygote comparison (OR=1.41, 95% CI=1.07-1.86, P=0.015), but not by that using the dominant model (OR=1.12, 95% CI=0.95-1.33, P=0.18). However, no significant association of XRCC3 Thr241Met polymorphism with the risk of thyroid cancer was found in individual ethnic subgroups. CONCLUSIONS We conclude that the XRCC3 Thr241Met polymorphism is associated with an increased risk of thyroid cancer in the overall population, while no significant association was observed in individual ethnic subgroups due to limited population size.
| S-EPMC4692576 | biostudies-literature
Project description:BackgroundPrevious studies suggest that the X-ray repair cross-complementing group 3 gene (XRCC3) Thr241Met genetic variant could be potentially associated with the risk of prostate cancer. However, results from these published studies were conflicting rather than conclusive.Objectiveshis meta-analysis aimed to conduct a better understanding of the effects of XRCC3 Thr241Met genetic variant on prostate cancer risk.MethodsWe identified three eligible studies, 499 prostate cancer cases and 571 controls.ResultsOverall, significant associations were detected in the heterozygote comparison genetic model (CT versus (vs.) CC: OR = 0.71, 95% CI 0.53-0.94, Z =2.38, p= 0.017), and the dominant genetic model (TT/CT vs. CC: OR = 0.74, 95% CI 0.57-0.98, Z = 2.11, p =0.035). In the subgroup analysis by ethnicities, we found that this genetic variant was significantly associated with the decrease risk of prostate cancer in Caucasians for heterozygote comparison genetic model (CT vs. CC: OR = 0.66, 95% CI 0.44-0.98, Z = 2.04, p = 0.042). No publication bias was found in this study.ConclusionsResults from this meta-analysis indicate that the XRCC3 Thr241Met genetic variant is associated with prostate cancer risk.
| S-EPMC4370129 | biostudies-literature
Project description:INTRODUCTION: X-ray repair cross-complementing protein 3 (XRCC3) is an essential gene involved in the double-strand break repair pathway. Published evidence has shown controversial results about the relationship between XRCC3 Thr241Met polymorphism and clinical outcomes of non-small cell lung cancer (NSCLC) patients receiving platinum-based chemotherapy. METHODS: A systematic review and meta-analysis was performed to evaluate the predictive value of XRCC3 Thr241Met polymorphism on clinical outcomes of advanced NSCLC receiving platinum-based chemotherapy. Response to chemotherapy, overall survival (OS) and progression-free survival (PFS) were analyzed. RESULTS: A number of 11 eligible studies were identified according to the inclusion criteria. Carriers of the variant XRCC3 241Met allele were significantly associated with good response to platinum-based chemotherapy (ThrMet/MetMet vs. ThrThr: OR ?=?1.509, 95% CI: 1.099-2.072, Pheterogeneity ?=?0.618). The XRCC3 Thr241Met polymorphism was not associated with OS (MetMet vs. ThrThr, HR ?=?0.939, 95% CI:0.651-1.356, Pheterogeneity ?=?0.112) or PFS (MetMet vs. ThrThr, HR ?=?0.960, 95% CI: 0.539-1.710, Pheterogeneity ?=?0.198). Additionally, no evidence of publication bias was observed. CONCLUSIONS: This systematic review and meta-analysis shows that carriers of the XRCC3 241Met allele are associated with good response to platinum-based chemotherapy in advanced NSCLC, while the XRCC3 Thr241Met polymorphism is not associated with OS or PFS.
| S-EPMC3734199 | biostudies-other
Project description:Background: The Leu72Met polymorphism of ghrelin gene has been associated with genetic predisposition to type 2 diabetes mellitus (T2DM), while conclusions remain conflicting. Hence, we performed this updated meta-analysis to clarify the association between Leu72Met polymorphism and T2DM susceptibility. Methods: Six electronic databases were consulted for articles published before 1 January, 2018. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated under five genetic models to assess this association. We used I 2-test and Q statistics to measure heterogeneity across the included studies. Subgroup analyses and publication bias were also performed. Results: Thirteen case-control studies involving 4720 T2DM patients and 4206 controls were included in this meta-analysis. The overall results using fixed-effects models showed that Leu72Met polymorphism was significantly associated with an increased risk of T2DM under homozygous model (OR = 1.307, 95%CI 1.001-1.705, p = 0.049). Further subgroup analyses stratified by ethnicity revealed that the risk for T2DM was only increased in Asians (homozygous model: OR = 1.335, 95%CI 1.014-1.758, p = 0.040), while decreased in Caucasians (dominant model: OR = 0.788, 95%CI 0.635-0.978, p = 0.030; heterozygous model: OR = 0.779, 95%CI 0.626-0.969, p = 0.025; allelic model: OR = 0.811, 95%CI 0.661-0.995, p = 0.045). Funnel plots were basically symmetrical, and all p-values of Egger's test under five genetic models were >0.050, which indicated no evidence of publication bias. Conclusions: Our results demonstrate that the Leu72Met polymorphism of ghrelin gene may be protective against T2DM in Caucasians, while predisposing to T2DM in Asians.
| S-EPMC6246653 | biostudies-literature
Project description:The DNA repair gene, X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism may be associated with a susceptibility to glioma. The present study aimed to investigate the association between the XRCC3 Thr241Met polymorphism and the potential susceptibility to gliomas. A hospital-based case-control study was conducted, which included a total of 886 patients with glioma and 886 healthy control subjects. Peripheral blood samples were extracted and the polymerase chain reaction-restriction fragment length polymorphism method was performed to analyze the genotypes. The glioma patients had a significantly higher frequency of the XRCC3 241 MetMet genotype [odds ratio (OR) = 1.62; 95% confidence interval (CI): 1.09-2.41; P=0.02] compared with the control subjects. When stratified by the grade of the glioma, the patients with stage IV glioma (according to the World Health Organization classification) had a significantly higher frequency of the XRCC3 241 MetMet genotype (OR=1.61; 95% CI: 1.06-2.44; P=0.03). When stratified by the histology of the glioma, there was no significant difference in the distribution of each genotype. The findings of the present study indicate that the XRCC3 Thr241Met polymorphism is associated with a susceptibility to glioma.
| S-EPMC4081356 | biostudies-literature
Project description:BACKGROUND:X-ray repair cross-complementing group 3 (XRCC3) plays a crucial role in mammalian DNA repair processes. The polymorphism of XRCC3, rs861539 (Thr > Met at codon 241), is common in populations worldwide. This study analyzed the relationship between this functional single nucleotide polymorphism and systemic lupus erythematosus (SLE) in the Han Chinese population in Taiwan (HC-TW). METHODS:Genotyping was performed using polymerase chain reaction restriction fragment length polymorphism on 163 SLE patients and 191 healthy participants in the control group. RESULTS:The data showed that the genotype frequency at codon 241 did not differ significantly between the SLE patients and the healthy participants in the control group; however, the allele frequency analysis indicated a significant difference between these groups. In addition, we used the genotype and allele frequencies of 191 healthy HC-TW participants for comparison with HapMap populations. The results indicated a significant difference of XRCC3 Thr241Met allele and genotype frequencies between the HC-TW population and HapMap populations, except for the other Han Chinese populations. A prior study showed that Thr241 > Met substitution in XRCC3 protein was positive as damaging and functional consequences as well. CONCLUSION:This is the first study to demonstrate the difference of XRCC3 Thr241 > Met variant between the HC-TW population and HapMap population.
| S-EPMC6807594 | biostudies-literature
Project description:DNA repair systems are essential for cellular functions. Defects due to sequence variations in DNA repair genes can lead severe failure of cell functions and causing many cancer types including leukemia. The aim of this study was to investigate the relationship between XRCC1 Arg399Gln and XRCC3 Thr241Met polymorphisms and susceptibility to chronic lymphocytic leukemia (CLL) in Turkish patients. In addition, genotype distribution of these polymorphisms was compared with other populations. The frequencies of Arg399Gln and Thr241Met single nucleotide polymorphisms were studied in 25 CLL patients and 30 healthy individuals. Single nucleotide polymorphisms were genotyped by PCR-RFLP method. The genotype and allele frequencies of Arg399Gln and Thr241Met polymorphisms were not statistically different between the CLL patients and control group. The allelic frequency similarities were found between Turkish and Brazilian populations for Arg399Gln polymorphism. On the other hand, similarities were found between Turkish and other Caucasian populations for Thr241Met polymorphism. Marked differences were observed between American African versus Turkish and Chinese versus Turkish populations for Arg399Gln and Thr241Met polymorphisms respectively. These results indicate that Arg399Gln and Thr241Met polymorphisms were not associated with the development of CLL in Turkish population and ethnic differences is one of the most important factor for allele frequency differences.
| S-EPMC4465508 | biostudies-literature
Project description:BACKGROUND:The X-ray repair cross-complementing group 3 (XRCC3) is an efficient component of homologous recombination and is required for the preservation of chromosomal integrity in mammalian cells. The association between Thr241Met single-nucleotide polymorphism (SNP) in this gene and susceptibility to breast cancer has been assessed in several studies. Yet, reports are controversial. The present meta-analysis has been designed to identify whether this SNP is associated with susceptibility to breast cancer. METHODS:We performed a systematic review and meta-analysis for retrieving the case-control studies on the associations between T241?M SNP and the risk of breast cancer. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to verify the association in dominant, recessive, and homozygote inheritance models. RESULTS:We included 55 studies containing 30,966 sporadic breast cancer cases, 1174 familial breast cancer cases and 32,890 controls in the meta-analysis. In crude analyses, no association was detected between the mentioned SNP and breast cancer risk in recessive, homozygote or dominant models. However, ethnic based analysis showed that in sporadic breast cancer, the SNP was associated with breast cancer risk in Arab populations in homozygous (OR (95% CI)?=?3.649 (2.029-6.563), p?=?0.0001) and recessive models (OR (95% CI)?=?4.092 (1.806-9.271), p?=?0.001). The association was significant in Asian population in dominant model (OR (95% CI)?=?1.296, p?=?0.029). However, the associations was significant in familial breast cancer in mixed ethnic-based subgroup in homozygote and recessive models (OR (95% CI)?=?0.451 (0.309-0.659), p?=?0.0001, OR (95% CI)?=?0.462 (0.298-0.716), p?=?0.001 respectively). CONCLUSIONS:Taken together, our results in a large sample of both sporadic and familial cases of breast cancer showed insignificant role of Thr241Met in the pathogenesis of this type of malignancy. Such results were more conclusive in sporadic cases. In familial cases, future studies are needed to verify our results.
| S-EPMC6511159 | biostudies-literature