X-ray Repair Cross-complementing Group 3 Thr241Met Polymorphism Research Articles

Ethnicity-stratified analysis of the association between XRCC3 Thr241Met polymorphism and leukemia: an updated meta-analysis

BackgroundPresently, 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.MethodsTwo 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.ResultsOverall, 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).ConclusionsThe present meta-analysis suggests that the XRCC3 Thr241Met polymorphism may be a risk factor for leukemia in Caucasian population.

A literature review and systematic meta-analysis on XRCC3 Thr241Met polymorphism associating with susceptibility of oral cancer.

Oral cancer is very common, occurring on head as well as neck region with poor prognosis. The X-ray repair cross-complementing group 3 (XRCC3) gene contained in DNA repairing pathway has been investigated for its functional role in oral cancer. Nevertheless, the corresponding results are inconclusive. This study investigated the association of XRCC3 Thr241Met polymorphism regarding oral cancer risk. Article and literature searches were performed using Embase, Medline, PubMed, Wanfang and China National Knowledge Infrastructure (CNKI) databases with a manual search. The keywords of ‘XRCC3 or X-ray repair cross complementing protein 3’, ‘polymorphism or SNP’, ‘oral cancer or oral squamous cell carcinoma’ and their combinations were used to search literature. In accordance with the criteria of inclusion, we focused on only case-and-control studies with the distribution of genotypes and alleles being available to be extracted. Systematic meta-analysis was conducted via the STATA software (version 11.0). After a comprehensive literature collection and review, 1,615 oral cancer cases and 1,897 matched controls extracted from 7 articles were included for this meta-analysis. Our results show that only Met/Met (TT) genotype with the recessive model was associated with high risk of oral cancer (CC + CT vs. TT, OR=1.81, P=0.001, 95% CI=1.28–2.567). A significant relationship was identified under both homozygous and recessive model in Asians (CC vs. TT: OR=2.15, 95% CI=1.107–4.170, P=0.024; CT + CC vs. TT: OR=2.140, 95% CI=1.105–4.144, P=0.024), but not among Caucasians (P>0.05). The results indicate that XRCC3 241Met allele might be a potential factor for oral cancer risk, particularly among Asian population. A further study using a larger population and more ethnicities should be performed to confirm the findings.

Associations between XRCC3 Thr241Met polymorphisms and breast cancer risk: systematic-review and meta-analysis of 55 case-control studies

BackgroundThe 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.MethodsWe 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.ResultsWe 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).ConclusionsTaken 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.

3. X-ray repair cross complementing group 3 polymorphism in association with aflatoxin B1 exposure in chronic hepatitis (B & C) and hepatocellular carcinoma

Background and Aims: X-ray repair cross-complementing group 3 (XRCC3) is a constituent of DNA repair genes involved in the process of DNA double-strand breaks repair pathway. XRCC3 Thr241Met (C > T) polymorphism is a single nucleotide polymorphism (SNP) at codon 241 in exon 7. We aimed to study polymorphisms of XRCC3 Thr241Met in Chronic Hepatitis (B & C) and Hepatocellular carcinoma patients and healthy individuals. This was correlated with total aflatoxin content in various indigenous foods consumed by general population and chronic liver disease patients from Assam, India. Methods: We conducted a hospital based case control study including 70 Chronic Hepatitis (B & C) cases and 70 healthy controls, alongwith 20 Hepatocellular Carcinoma cases and 20 healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR- RFLP) assay in Assamese population. Results: Out of 70 cases of chronic liver disease (HBV & HCV) 67.14% patients showed SNP for XRCC3 Thr241Met out of which 32.85% were homozygous (C/C), 50% were heterozygous (C/T) and 17.14% were mutated (T/T). Whereas out of 20 Hepatocellular carcinoma cases 30% were homozygous (C/C), 35% were heterozygous (C/T) and 35% were mutated (T/T). No significant association of SNP's was observed with duration of alcohol consumption, raised transaminase, low platelet count, HBsAg and Anti HCV status. The indigenous food samples were examined by HPLC technique which did not reveal significant aflatoxin content. Conclusions: The XRCC3 codon 241 polymorphism displayed a relationship with HCC and in chronic hepatitis B & C. Codon 241 mutation was significantly increased in patients of HCC and in chronic HBV or HCV. There is increased risk for the individuals with XRCC3 CT genotype [OR = 2.43 (1.17–5.03), p = 0.01*] and TT genotype [OR = 4.17 (1.30–13.34), p = 0.01*]. Hence, presence of mutation in the codon of XRCC3 TT genotype in patients of chronic HBV and HCV could indicate the likelihood of progression to HCC. The authors have none to declare.

Association between XRCC3 Thr241Met polymorphism and nasopharyngeal carcinoma risk: evidence from a large-scale case-control study and a meta-analysis

The X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism (rs861539, C>T) has drawn wide attentions as its association with cancer risk and its involvement in DNA repair. Several studies have attempted to link rs861539 to nasopharyngeal cancer (NPC) risk; however, the sample sizes of these studies are small and the results are controversial. To investigate the relationship of rs861539 and NPC susceptibility, we conducted a large-scale case-control study involving 4001 NPC cases and 2967 controls of southern Chinese. Logistic regression analysis revealed significant association for rs861539 and NPC risk under the recessive model (TT vs. CT+CC) with adjustment of age and gender (odds ratio, OR =2.72; 95% CI 1.10-6.72; P=0.03). Further, meta-analysis involving 4457 NPC cases and 4132 controls from four studies showed consistent association of TT carriers and NPC risk (OR=3.12; 95% CI 1.58-6.13; P=0.001). Taken together, our findings based on large-scale sample size suggested rs861539 at XRCC3 to be associated with NPC risk through recessive model.

Association between the XRCC3 Thr241Met Polymorphism and Gastrointestinal Cancer Risk: A Meta-Analysis

Background:The x-ray repair cross-complementing group 3 (XRCC3) encodes a protein involved in the homologous recombination repair (HRR) pathway for double-strand DNA repair. Associations of the XRCC3 Thr241Met polymorphism with various cancers have been widely reported. However, published data on links between XRCC3 Thr241Met and gastrointestinal (GI) cancer risk are inconsistent.Objective and Methods:A meta-analysis was conducted to characterize the relationship between XRCC3 Thr241Met polymorphisms and GI cancer risk. Pooled odds ratios (ORs) and 95.0% confidence intervals were assessed using random- or fixed- effect models for 28.0 relevant articles with 30.0 studies containing 7,649.0 cases and 11,123.0 controls.Results:The results of the overall meta-analysis suggested a borderline association between the XRCC3 Thr241Met polymorphism and GI cancer susceptibility (T vs. C: OR=1.18, 9 % CI=1.0–1.4, POR=0.04; TT vs. CT+CC: OR=1.3, 95 % CI=1.0–1.6, POR=0.04). After removing studies not conforming to Hardy–Weinberg equilibrium (HWE), however, this association disappeared (T vs. C: OR=1.00, 95 % CI=0.9–1.1, POR=0.96; TT vs. CT+CC: OR=0.9, 95 % CI=0.8–1.1, POR=0.72). When stratified by ethnicity, source of controls or cancer type, although some associations between XRCC3 Thr241Met polymorphism and GI cancer susceptibility were detected, these associations no longer existed after removing studies not conforming to HWE.Conclusion:Our meta-analysis suggests that the XRCC3 Thr241Met polymorphism is not associated with risk of GI cancer based on current evidence.

Association between the XRCC3 Thr241Met polymorphism and risk of colorectal cancer: a meta analysis of 5,193 cases and 6,645 controls.

Many studies have reported associations of the X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism with colorectal cancer (CRC) risk, but the results remained controversial. Hence, we performed the present meta-analysis with different inheritance models. We searched the PubMed and Google scholar databases for studies relating to associations between XRCC3 Thr241Met polymorphism and risk of CRC. 16 studies with 5,193 cases and 6,645 controls were finally included into the meta-analysis. We found that the XRCC3 Thr241Met polymorphism was associated with increased CRC risk only under a dominant genetic model (CC+CT vs. TT: OR 0.575, 95%CI 0.498-1.665, p<0.001, Pheterogeneity=0.00, I2=83%). There was a significant association between XRCC3 Thr241Met polymorphism and CRC risk in Caucasian in the overall 8 studies under only in the heterozygote genetic model (CT vs. TT: OR=0.929, 95%CI=0.806-1.070, P=0.308, Pheterogeneity=0.002, I2=57%). Four studies evaluated the XRCC3 Thr241Met polymorphism and CRC risk in Asians. Two genetic models of the XRCC3 polymorphism were significantly correlated with increasing risk in Asians (dominant model: CC+CT vs. TT: OR= 0.609, 95%CI=411-0.902, P=0.013, Pheterogeneity=0.54, I2=0.00%; Allele model: C vs. T: OR=0.708, 95 %=CI 0.605-0.829, p=0.000, Pheterogeneity=0.000, I2=92%). The sensitivity analysis suggested stability of this meta-analysis and no publication bias was detected. In conclusion, this meta-analysis indicates that XRCC3 Thr241Met shows an increased CRC risk, particularly in Asians rather than Caucasians.

DNA repair gene XRCC3 Thr241Met polymorphisms and lung cancer risk: A meta-analysis

The X-ray repair cross-complementing group 3 (XRCC3) is a highly suspected candidate gene for cancer susceptibility, and a large amount studies have examined the association of the rs861539 in XRCC3 (Thr241Met) with lung cancer risk in various populations. However, the results remain inconclusive. The electronic database of PubMed, Medline, Embase and CNKI (China National Knowledge Infrastructure) were searched for case-control studies published up to December 05, 2013. A systematic review and meta-analysis was performed to evaluate the relationship between XRCC3 Thr241Met polymorphism and lung cancer risk. Data were extracted and pooled odds ratio (OR) with its 95% confidence intervals (CI) were calculated. Total 21 studies, including 6880 lung cancer cases and 8329 controls, were available for meta-analysis. Overall, our results showed that the XRCC3 Thr241Met polymorphism was not associated with risk of lung cancer in all genetic contrast models (P>0.05). Stratified analyses by ethnicity (Asians, Caucasians and mixed population) showed similar results. Additionally, no evidence of publication bias was observed by using the funnel plot. There is no clear evidence showing a significant correlation between XRCC3 Thr241Met polymorphism and lung cancer risk in total population and stratified analysis by ethnicity. However, studies assessing the gene-gene interactions should be considered to further estimate this gene variant in lung cancer risk.

Association between XRCC3 Thr241Met Polymorphism and Risk of Breast Cancer: Meta-Analysis of 23 Case-Control Studies.

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/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.

Association between XRCC3 Thr241Met polymorphism and laryngeal cancer susceptibility in Turkish population.

DNA repair systems are essential for normal cell function. Genetic alterations in the DNA repair genes such as X-ray repair cross-complementing group 3 (XRCC3), can cause a change in protein activity which results in cancer susceptibility. The aim of this study was to investigate the association of XRCC3 Thr241Met single nucleotide polymorphism (SNP), smoking and alcohol consumption with the risk of laryngeal cancer in Turkish population. The frequencies of Thr241Met SNP were studied in 58 laryngeal cancer cases (SSC) and 67 healthy individuals. Genomic DNA was isolated from peripheral blood samples of both controls and laryngeal cancer cases. Thr241Met SNP was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The genotype and allele frequencies of Thr241Met polymorphism were not statistically significant between the laryngeal cancer and control groups. Carrying mutant allele was not associated with the risk of laryngeal cancer. On the other hand, smoking and chronic alcohol consumption were associated with the risk of laryngeal cancer but there is no association between Thr241Met, smoking and alcohol consumption in laryngeal cancer cases. These results indicate that Thr241Met polymorphism was not associated with the development of laryngeal cancer in Turkish population. However, it should be kept in mind that the association of a polymorphism with cancer susceptibility can differ due to several factors such as cancer type, selection criteria, ethnic differences and size of the studied population.

Association between the XRCC3 Thr241Met Polymorphism and Breast Cancer Risk: an Updated Meta-analysis of 36 Case-control Studies

The X-ray repair cross-complementing group 3 (XRCC3) is a highly suspected candidate gene for cancer susceptibility. Attention has been drawn upon associations of the XRCC3 Thr241Met polymorphism with breast cancer risk. However, the previous published findings remain controversial. Hence, we performed a meta-analysis to accurately evaluate any association between breast cancer and XRCC3 T241M (23, 812 cases and 25, 349 controls) in different inheritance models. PubMed and Web of Science databases were searched systematically until December 31, 2013 to obtain all the records evaluating the association between the XRCC3 Thr241Met polymorphism and breast cancer risk. Crude odds ratios (ORs) together with 95% confidence intervals (CIs) were used to assess the strength of associations. When all eligible studies were pooled into the meta analysis of XRCC3 T241M polymorphism, a significantly increased breast cancer risk was observed in heterozygote comparison (OR=1.06, 95%CI=1.01-1.12). No significant associations were found in other models. In subgroup analysis, this polymorphism seemed to be associated with elevated breast risk in Asians. No publication bias was detected. This meta-analysis suggests that the T241M polymorphism confers a weakly increased breast cancer risk. A study with the larger sample size is needed to further evaluate gene-gene and gene-environment interactions of the XRCC3 T241M polymorphism with breast cancer risk.

DNA repair gene XRCC3 Thr241Met polymorphism and susceptibility to glioma: A case-control study.

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.

No association between XRCC3 Thr241Met and XPD Lys751Gln polymorphisms and the risk of colorectal cancer in West Algerian population: a case–control study

Colorectal cancer (CRC) is a complex and multifactorial disease, in which genetic and environmental factors both seem to play a part. Many epidemiological studies have explored the association between genetic polymorphisms of X-ray repair cross-complementing group 3 (XRCC3) (Thr241Met) and Xeroderma pigmentosum group D (XPD) lysine to glutamine at codon 751 (Lys751Gln) and risk of CRC in various populations; however, the results are controversial. We conducted this case-control study in a West Algerian population to assess the potential role of this genetic polymorphism on the risk of CRC in this population. Genomic DNA was extracted from blood samples collected from 129 sporadic CRC patients and 148 normal controls. The polymorphisms were determined by pyrosequencing technique. The distribution of XRCC3 Thr241Met and XPD Lys751Gln genotypes among controls did not differ significantly from those predicted by the Hardy-Weinberg distribution (p > 0.05). There were no significant differences in the genotypes distribution and allele frequencies between CRC patients and controls. A significant association was found between the combined heterozygous of XRCC3 and homozygous variant of XPD gene and CRC. This is the first study on DNA repair genetic polymorphisms in West Algerian population, and it suggests that the XRCC3 Thr241Met and XPD Lys751Gln polymorphisms may not be associated with the CRC risk in this population.

Polymorphisms in DNA repair genes (APEX1, XPD, XRCC1 and XRCC3) and risk of preeclampsia in a Mexican mestizo population.

Variations in genes involved in DNA repair systems have been proposed as risk factors for the development of preeclampsia (PE). We conducted a case-control study to investigate the association of Human apurinic/apyrimidinic (AP) endonuclease (APEX1) Asp148Glu (rs1130409), Xeroderma Pigmentosum group D (XPD) Lys751Gln (rs13181), X-ray repair cross-complementing group 1 (XRCC) Arg399Gln (rs25487) and X-ray repair cross-complementing group 3 (XRCC3) Thr241Met (rs861539) polymorphisms with PE in a Mexican population. Samples of 202 cases and 350 controls were genotyped using RTPCR. Association analyses based on a χ2 test and binary logistic regression were performed to determine the odds ratio (OR) and a 95% confidence interval (95% CI) for each polymorphism. The allelic frequencies of APEX1 Asp148Glu polymorphism showed statistical significant differences between preeclamptic and normal women (p = 0.036). Although neither of the polymorphisms proved to be a risk factor for the disease, the APEX1 Asp148Glu polymorphism showed a tendency of association (OR: 1.74, 95% CI = 0.96–3.14) and a significant trend (p for trend = 0.048). A subgroup analyses revealed differences in the allelic frequencies of APEX1 Asp148Glu polymorphism between women with mild preeclampsia and severe preeclampsia (p = 0.035). In conclusion, our results reveal no association between XPD Lys751Gln, XRCC Arg399Gln and XRCC3 Thr241Met polymorphisms and the risk of PE in a Mexican mestizo population; however, the results in the APEX1 Asp148Glu polymorphism suggest the need for future studies using a larger sample size.

Association of XRCC3 Thr241Met polymorphism and leukemia risk: evidence from a meta-analysis

The relationship between the X-ray repair cross-complementing group 3 (XRCC3) Thr241Met (rs861539) polymorphism and the risk of leukemia remains inclusive or controversial. For a better understanding of the effect of XRCC3 Thr241Met (rs861539) polymorphism on leukemia risk, we performed a meta-analysis. All eligible studies were identified through a search of PubMed, Excerpta Medica Database (Embase) and the Chinese Biomedical Literature Database (CBM) up to August 2013. The association between the XRCC3 Thr241Met (rs861539) polymorphism and leukemia risk was analyzed by means of odds ratios (ORs) and 95% confidence intervals (CI). Ultimately, seven studies with 1070 cases and 1850 controls were included in the meta-analysis. There was no association between Thr241Met polymorphism and leukemia risk in any of the five models in the overall populations (T vs. C: OR = 1.43, 95% CI = 0.95–2.13, p = 0.086; TT vs. CC: OR = 1.71, 95% CI = 0.88–3.33, p = 0.112; TC vs. CC: OR = 1.35, 95% CI = 0.96–1.91, p = 0.089; TT vs. TC/CC: OR = 1.59, 95% CI = 0.87–2.89, p = 0.132; TT/TC vs. CC: OR = 1.37, 95% CI = 0.98–1.94, p = 0.070). In subgroup analysis according to ethnicity, a significant association was found between XRCC3 Thr241Met (rs861539) polymorphism and leukemia risk in Asian but not in Caucasian or mixed populations. In conclusion, the results suggest no association between XRCC3 Thr241Met (rs861539) polymorphism and leukemia risk in the overall populations but a significant association between XRCC3 Thr241Met (rs861539) polymorphism and leukemia risk in the Asian population. Considering the limited sample size and ethnicities included in the meta-analysis, further large-scale, well-designed studies are needed to confirm our results.

XRCC3 Thr241Met polymorphism and gastric cancer susceptibility: A meta-analysis

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 genetic models. When stratifying for race, we found the 241Met/Met genotype carriers might be at high risk of GC among Asians, but not among Caucasians. When stratifying by the location of gastric cancer, the combined results showed that Met/Met genotype carriers might have an increased risk of GC in non-cardiac gastric cancer, but not in cardiac cancer. This meta-analysis confirmed that the XRCC3 Thr241Met gene polymorphism might be a risk factor for GC among Asians, and that differences in genotype distribution may be related to the location of gastric cancer. More well-designed studies based on larger population are needed to confirm our results.

XRCC3 Thr241Met polymorphism and ovarian cancer risk: a meta-analysis

Genetic 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/CC: OR = 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.

XRCC3 Thr241Met Is Associated with Response to Platinum-Based Chemotherapy but Not Survival in Advanced Non-Small Cell Lung Cancer

BackgroundA lot of studies have investigated the correlation between x-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism and clinical outcomes in non-small cell cancer (NSCLC), while the conclusion is still conflicting.Materials and MethodsWe conducted this meta-analysis to evaluate the predictive value of XRCC3 Thr241Met polymorphism on response and overall survival of patients with NSCLC. Pooled odds ratios (ORs) and hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs) were used to estimate the association strength.ResultsA total of 14 eligible studies with 2828 patients were identified according to our inclusion criteria. Meta-analysis results showed that carriers of the variant 241Met allele were significantly associated with good response, compared with those harboring the wild 241Thr allele (Met vs. Thr, OR = 1.453, 95% CI: 1.116–1.892, Pheterogeneity = 0.968 and ThrMet+MetMet vs. ThrThr, OR = 1.476, 95% CI: 1.087–2.004, Pheterogeneity = 0.696). This significant association was observed in Caucasian population but not in Asian population. On the other hand, there was no significant association of XRCC3 Thr241Met polymorphism with survival (ThrMet+MetMet vs. ThrThr, HR = 1.082, 95% CI: 0.929–1.261, Pheterogeneity = 0.564), and there was no difference between Asian and Caucasian population.ConclusionsThese findings suggest a predictive role of XRCC3 Thr241Met polymorphism on response to platinum-based chemotherapy in patients with advanced NSCLC. Additionally, we first report that the XRCC3 Thr241Met polymorphism is associated with response to platinum-based chemotherapy and highlights the prognostic value of the XRCC3 Thr241Met polymorphism.

Association between XRCC3 Thr241Met polymorphism and risk of brain tumors: a meta-analysis

X-ray repair cross-complementing group 3 (XRCC3) plays an important role in the process of homologous recombination repair for DNA double-strand breaks which further maintains the stability of the genome. XRCC3 Thr241Met polymorphism has been indicated in the development of cancers, but the association of the XRCC3 Thr241Met polymorphism with risk of brain tumors is still unclear owing to the conflicting findings from previous studies. We performed a meta-analysis to provide a better understanding on the association between the XRCC3 Thr241Met polymorphism and risk of brain tumors. The pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was used to assess the association. Thirteen case-control studies involving a total of 4,984 cases and 7,472 controls were included. Overall, there was no statistically significant association between the XRCC3 Thr241Met polymorphism and risk of brain tumors under all contrast models. Subgroup analysis by race suggested that the XRCC3 Thr241Met polymorphism was associated with increased risk of brain tumors in Asians under all four contrast models (Met vs. Thr: OR = 1.22, 95 % CI 1.09-1.36, P < 0.01; MetMet vs. ThrThr: OR = 1.89, 95 % CI 1.38-2.57, P < 0.01; MetMet vs. ThrThr/ThrMet: OR = 1.78, 95 % CI 1.31-2.40, P < 0.01; and MetMet vs. ThrThr/ThrMet: OR = 1.19, 95 % CI 1.04-1.36, P = 0.01). However, there was no significant association between the XRCC3 Thr241Met polymorphism and risk of brain tumors in Caucasians. Therefore, the XRCC3 Thr241Met polymorphism is associated with increased risk of brain tumors, especially in Asians.

Predictive effect of XRCC3 Thr241Met polymorphism on platinum-based chemotherapy in lung cancer patients: meta-analysis

Previous published data on the association between X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism and clinical outcome of platinum-based chemotherapy in patients with lung cancer reported conflicting results. A meta-analysis was performed to provide a systematic review of the published data. We retrieved the relevant studies from PubMed and Embase databases. The primary outcome was overall survival, and the hazard ratio (HR) with 95% confidence interval (95% CI) was estimated. Seven studies with a total of 1,514 patients were included into the meta-analysis. Overall, XRCC3 Thr241Met polymorphism had no influence on the overall survival of lung cancer patients receiving platinum-based chemotherapy (MetMet vs. ThrThr: HR = 0.82, 95% CI 0.52-1.31, P = 0.410; MetThr vs. ThrThr: HR = 0.93, 95% CI 0.79-1.10, P = 0.339; MetMet/MetThr vs. ThrThr: HR = 1.07, 95% CI 0.88-1.31, P = 0.480). There was no obvious risk of publication bias. Therefore, currently available data suggest that there is no predictive effect of XRCC3 Thr241Met polymorphism on platinum-based chemotherapy in lung cancer patients.