Correlation between Selected XRCC2, XRCC3 and RAD51 Gene Polymorphisms and Primary Breast Cancer in Women in Pakistan

Genetic polymorphisms in homologous recombination repair genes cause an abnormal development ofcancerous cells. In the present study we evaluated the possibility of breast cancer association with single nucleotidepolymorphisms of RAD51, XRCC2 and XRCC3 genes. Polymorphisms selected in this study were RAD51 135G/C,XRCC2 Arg188His; and XRCC3 Thr241Met. Each polymorphism was genotyped using Polymerase chainreaction-restriction fragment length polymorphism in study cohort of 306 females (156 breast cancer patientsand 150 controls). We observed that heterozygous variant genotype (GC) of RAD51 135 G/C polymorphism wasassociated with a significantly (OR=2.70; 95%CI (0.63-1.79); p<0.03) increased risk of breast cancer. In caseof the XRCC3 gene we observed that frequency of heterozygous (OR=2.88; 95%CI (1.02-8.14); p<0.02) andhomozygous (OR=1.46; 95%CI (0.89-2.40); p<0.04) genotype of Thr241Met polymorphism were significantlyhigher in breast cancer patients. For the Arg188His polymorphism of XRCC2, ~2fold increase in breast cancerrisk (OR=1.6, 95%CI = 0.73-3.50) was associated with GA genotype with a p value for trend of 0.03. Our resultssuggest that the 135G/C polymorphism of the RAD51, Thr241Met polymorphism of XRCC3 and Arg188Hispolymorphism of XRCC2 can be independent markers of breast cancer risk in Pakistan.     

XPG Asp1104His,XRCC2 rs3218536 A/G and RAD51 135G/C gene polymorphisms and colorectal cancer risk: A meta-analysis

Background: DNA repair mechanisms are crucial for sustaining DNA integrity and preventing carcinogenesis. The xeroderma pigmentosum group G (XPG), X-ray repair cross complementing group 2 (XRCC2) and RAD51 are candidate genes for DNA repair pathways. Methods: We performed a meta-analysis of 26 studies that assessed the impact of XPG Asp1104His, XRCC2 rs3218536 A/G and RAD51 135G/C polymorphisms on colorectal cancer (CRC) risk. This study included 10288 CRC patients and 11885 controls, and odds ratio (OR) with its 95% confidence interval (CI) were used to calculate the strength of association. Results: The results of overall meta-analysis suggested an association between the XPG Asp1104His polymorphism and CRC susceptibility in allele (OR=1.06; 95%CI=1.01-1.12) and heterozygote model (OR=1.16; 95%CI=1.02-1.31). In the subgroup analysis based on ethnicity and source of control, we found significantly increased CRC cancer risk in Asians (OR=1.12, 95%CI=1.04-1.21) and in hospital-based (OR=1.22, 95%CI=1.08-1.38) populations. Moreover, the RAD51 135 G/C polymorphism increased the risk of CRC in total using allele (OR=1.21) and recessive models (OR=1.62). However, XRCC2 rs3218536 A/G was not associated with the risk of CRC in total or in subgroups. Conclusions: According to the results of our meta-analysis, the XPG Asp1104His and RAD51 135 G/C polymorphisms might influence colorectal cancer risk.     

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.     

Variants in DNA double-strand break repair genes and risk of familial breast cancer in a South American population

The double-strand break (DSB) DNA repair pathway has been implicated in breast cancer (BC). RAD51 and its paralogs XRCC3 and RAD51D play an important role in the repair of DSB through homologous recombination (HR). Some polymorphisms including XRCC3-Thr241Met, RAD51-135G>C, and RAD51D-E233G have been found to confer increased BC susceptibility. In order to detect novel mutations that may contribute to BC susceptibility, 150 patients belonging to 150 Chilean BRCA1/2-negative families were screened for mutations in XRCC3. No mutations were detected in the XRCC3 gene. In addition, using a case–control design we studied the XRCC3-Thr241Met, and RAD51D-E233G polymorphisms in 267 BC cases and 500 controls to evaluate their possible association with BC susceptibility. The XRCC3 Met/Met genotype was associated with an increased BC risk (P = 0.003, OR = 2.44 [95%CI 1.34–4.43]). We did not find an association between E233G polymorphism and BC risk. We also analyzed the effect of combined genotypes among RAD51-135G>C, Thr241Met, and E233G polymorphisms on BC risk. No interaction was observed between Thr241Met and 135G>C. The combined genotype Thr/Met–E/G was associated with an increased BC risk among women who (a) have a family history of BC, (b) are BRCA1/2-negative, and (c) were <50 years at onset (n = 195) (P = 0.037, OR = 10.5 [95%CI 1.16–94.5]). Our results suggested that the variability of the DNA HR repair genes XRCC3 and RAD51D may play a role in BC risk, but this role may be underlined by a mutual interaction between these genes. These findings should be confirmed in other populations.     

Association between the XRCC3 Thr241Met Polymorphism and Risk of Colorectal Cancer: a Meta Analysis of 5,193 Cases and 6,645 Controls

Background: 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. Materials and Methods:We searched the PubMed and Google scholar databases for studies relating to associations between XRCC3Thr241Met polymorphism and risk of CRC. 16 studies with 5,193 cases and 6,645 controls were finally includedinto the meta-analysis. Results: We found that the XRCC3 Thr241Met polymorphism was associated withincreased 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 andCRC 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 Thr241Metpolymorphism and CRC risk in Asians. Two genetic models of the XRCC3 polymorphism were significantlycorrelated 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 wasdetected. Conclusions: In conclusion, this meta-analysis indicates that XRCC3 Thr241Met shows an increasedCRC risk, particularly in Asians rather than Caucasians.     

DNA repair polymorphisms might contribute differentially on familial and sporadic breast cancer susceptibility: a study on a Portuguese population

The purpose of this study was to evaluate the role of polymorphisms in DNA repair genes as genetic indicators of susceptibility to familial and sporadic breast cancer. We analysed DNA samples from 285 breast cancer patients and 442 control subjects, for XRCC1 Arg399Gln, XPD Lys751Gln, RAD51 G135C and XRCC3 Thr241Met polymorphisms using PCR-RFLP. We observed that women carriers of XRCC1 399Gln genotypes and without family history of breast cancer have a protective effect concerning this disease (OR = 0.54 95% CI 0.35–0.84; p = 0.006). Furthermore, we found that carriers of XRCC3 241Met genotypes without FH have an increased susceptibility of breast cancer (OR = 2.21 95% CI 1.42–3.44; p < 0.001). Additionally, we verified an increased risk of breast cancer in women with FH and carrying RAD51 135C genotypes (OR = 2.17 95% CI 1.19–3.98; p = 0.012). Our results suggest XRCC1 Arg399Gln and XRCC3 Thr241Met DNA repair polymorphisms as important biomarkers to sporadic breast cancer susceptibility, as well as, RAD51 G135C polymorphism as a real risk modifier in familial breast cancer cases.     

XRCC3Thr241Met基因多态性与胃癌易感性的Meta分析

目的:综合评价X线修复交叉互补基因3(X-ray repair cross-complementing group 3,XRCC3)Thr241 Met单核苷酸基因多态性与胃癌易感性的关系.方法:计算机检索中国期刊全文数据库(CNKI)、中国生物医学文献数据库(CBM)、中文科技期刊全文数据库(VIP)、万方数据库、PubMed、Cochrane Library,收集国内外公开发表的关于XRCC3 Thr241Met基因多态性与胃癌易感性的病例-对照研究相关文献.采用Stata 12.0软件进行统计学分析,计算合并比值比(odd ratio,OR)及95％可信区间(confidence interval,CI).结果:共纳入12篇文献,从总的效应量分析,XRCC3 Thr241 Met基因多态性与胃癌易感性间无明显相关性,按种族进行亚组分析,提示在亚洲人群中隐性模型(MM vs MT +TT:OR =2.59,95％ CI:1.98 ～ 3.39,P＜0.001)、等位模型(Mvs T:OR=1.57,95％ CI:1.05～2.35,P=0.028)、纯合子模型(MM vs TT:OR =3.39,95％ CI:2.17～5.31,P＜O.001)均具有统计学意义.基于对照组来源及是否符合Hardy-Weinberg遗传平衡进行的亚组分析结果提示突变型与野生型无明显统计学意义.结论:在亚洲人群中,XRCC3 Thr241 Met基因多态性可能与胃癌易感性有关.     

Genetic polymorphism of <Emphasis Type="Italic">XRCC3</Emphasis> Thr<Superscript>241</Superscript>Met and breast cancer risk: case-control study in Korean women and meta-analysis of 12 studies

To evaluate the relationship of genetic polymorphism in XRCC3 Thr²⁴¹Met and the risk of breast cancer, a hospital-based case-control study was conducted in Korea. Histologically confirmed breast cancer cases (n = 574) and controls (n = 502) with no present or previous history of cancer were recruited from several teaching hospitals in Seoul during 1995–2001. Information on demographic characteristics and other information were collected by interviewed questionnaire. Genetic polymorphisms of XRCC3 Thr²⁴¹Met (C > T) was determined by single base extention assay. The frequency of Thr/Thr, Thr/Met, and Met/Met genotype were 89.4, 10.4, 0.2% in cases and 92.3, 7.7, 0.0% in controls, respectively. Genotype distribution in controls fit well to the Hardy–Weinberg equilibrium (P = 0.74). XRCC3 codon 241 Thr/Met or Met/Met genotype moderately increased the risk of breast cancer (OR = 1.4, 95% CI: 0.87–2.33), but not significant in this study. In the results of meta-analysis using twelve reports, however, Thr/Met or Met/Met genotype increased the risk of breast cancer (OR = 1.08, 95%CI: 1.00–1.17). In conclusion, although the genetic polymorphism of XRCC3 Thr²⁴¹Met was unlikely to have a substantial overall association in Korean women, the meta-analysis of studies, including ours, provided that Thr/Met and Met/Met was weakly increased the risk of breast cancer compare to Thr/Thr genotype.     

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.     

Comment on: “Association Between the XRCC3 Thr241Met Polymorphism and Risk of Colorectal Cancer: A Meta-Analysis of 5,193 Cases and 6,645 Controls”

Dear editor We read with great interest the recent article by Namazi and colleagues, “association between the XRCC3 Thr241Met polymorphism and risk of colorectal cancer: a meta-analysis of 5,193 cases and 6,645 controls”(Namazi et al., 2015). There are some important negative points decrease the reliability of the article. Firstly, some contradictory findings exist in this meta-analysis. The author found a significant association between the XRCC3 Thr241Met polymorphism and colorectal cancer under the overall dominant and heterozygous model in Caucasian descent. Our review demonstrated inconsistent results in texture (CC+CT vs. TT: OR=0.575, 95%CI=0.498-1.665, P<0.001, Pheterogeneity=0.00, I2=83%) and diagram of overall dominant model (CC+CT vs. TT: OR=0.904, 95%CI=0.796-1.027, P=0.120). On the other hand, in a stratified analysis by ethnicity, the P value of heterozygous model in Caucasian descent is more than 0.05 (CT vs. TT: OR=0.929, 95%CI=0.806-1.070, P=0.308, Pheterogeneity=0.002, I2=57%). Therefore, it seems to exist no significant association between the XRCC3 Thr241Met polymorphism and colorectal cancer under mentioned genetic models. Moreover, the author reported that the dominant and allelic genetic models of the XRCC3 Thr241Met polymorphism were significantly correlated with increasing risk of CRC in Asian population (Dominant model: CC+CT vs. TT: OR=0.609, 95%CI=0.411-0.902, P=0.013, Pheterogeneity=0.54, I2=0.00%; Allelic model: C vs. T: OR=0.708, 95%CI=0.605-0.829, P=0.000, Pheterogeneity=0.000, I2=92%). Conversely, the OR of dominant and allelic models in Asian descent represent decreasing CRC risk.     

Association of XRCC3 Thr241Met Polymorphisms and Gliomas Risk: Evidence from a Meta-analysis

The relationship between the X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphismand gliomas remains inclusive or controversial. For better understanding of the effect of XRCC3 Thr241Metpolymorphism on glioma risk, a meta-analysis was performed. All eligible studies were identified through asearch of PubMed, Elsevier Science Direct, Excerpta Medica Database (Embase) and Chinese BiomedicalLiterature Database (CBM) before May 2013. The association between the XRCC3 Thr241Met polymorphismand gliomas risk was conducted by odds ratios (ORs) and 95% confidence intervals (95% CIs). A total of ninecase-control studies including 3,533 cases and 4,696 controls were eventually collected. Overall, we found thatXRCC3 Thr241Met polymorphism was significantly associated with the risk of gliomas (T vs. C: OR=1.10,95%CI=1.01-1.20, P=0.034; TT vs. CC: OR=1.30, 95%CI=1.03-1.65, P=0.027; TT vs. TC/CC: OR=1.29,95%CI=1.01-1.64, P=0.039). In the subgroup analysis based on ethnicity, the significant association was foundin Asian under four models (T vs. C: OR=1.17, 95%CI=1.07-1.28, P=0.00; TT vs. CC: OR=1.79, 95%CI=1.36-2.36, P=0.00; TT vs. TC/CC: OR=1.75, 95%CI=1.32-2.32, P=0.00; TT/TC vs. CC: OR=1.11,95% CI=1.02-1.20).This meta-analysis suggested that the XRCC3 Thr241Met polymorphism is a risk factor for gliomas, especiallyfor Asians. Considering the limited sample size and ethnicities included in the meta-analysis, further large scaleand well-designed studies are needed to confirm our results.     

DNA repair gene XRCC2 and XRCC3 polymorphisms and susceptibility to cancers of the upper aerodigestive tract

Cigarette smoke can generate reactive oxygen species, which are capable of inducing double-strand breaks (DSBs) in DNA. Polymorphisms in XRCC2 and XRCC3 genes, involved in DSBs repair pathways, may alter an individual's susceptibility to smoking-related cancers. We investigated the effect of XRCC2 Arg(188)His and XRCC3 Thr(241)Met polymorphisms in cancer proneness in 121 oral/pharynx cancer cases, 129 larynx cancer cases and 172 noncancer controls, all Caucasian smokers. The XRCC2 His-allele was associated with a significantly increased risk of pharyngeal cancer (OR=2.9, 95% CI: 1.3-6.2). No significant associations were observed between the XRCC3 Thr(241)Met polymorphism and overall risk of developing UADT cancers. However, quite opposite to the expectations, a reduced risk of supraglottic cancer was found for carriers of the XRCC3 Met variant allele (OR=0.3, 95% CI: 0.2-0.7). These findings provide evidence for the view that polymorphisms in DNA repair genes may modify individual susceptibility to smoking-related cancers.     

DNA损伤修复基因XRCC3 Thr241Met多态与肺癌易感性关系的Meta分析

目的:探讨DNA损伤修复基因X射线交叉互补修复基因3(XRCC3)Thr241Met多态性与肺癌易感性的关系。方法:查找中国医学文献数据库和PubMed,以得到XRCC3基因Thr241Met多态与肺癌易感性关系的病例-对照研究,根据纳入和排除标准筛选符合条件的研究进行Meta分析,合并XRCC3基因Thr241Met多态与肺癌易感性关系的OR值,然后进行亚组分析、敏感性分析和文献的发表偏倚检验。结果:本次Meta分析共纳入13篇文献,累计病例2 986例,对照4 495例,显性模型下TM+MM基因型相对于TT(TM=Thr/Met)基因型OR值为0.96(95%CI为0.86~1.06),差异无统计学意义。结论:尚无足够证据证明XRCC3基因Thr241Met多态同肺癌易感性有关。     

An association of polymorphism of DNA repair genes XRCC1 and XRCC3 with colorectal cancer

Variability in DNA repair genes may contribute to human cancer risk. We performed a case-control study (51 cases and 100 controls) to test the association between two polymorphisms: Arg399Gln in the XRCC1 gene and Thr241Met in the XRCC3 gene and colorectal cancer risk. Genotypes were determined in tumour tissue and distant mucosa samples by PCR RFLP with the NciI restriction enzyme for XRCC1 and NcoI for XRCC3. Cancer occurrence was strongly associated with the XRCC3 Met/Met polymorphic variant (OR = 9.45; (95% CI 8.77-11.65)), whereas Thr/Thr and Thr/Met variants were associated with significant reduction in colorectal cancer risk (OR = 0.16; 95% CI 0-0.26 and OR = 0.26; 95% CI 0.25-0.27, respectively). Weak association was found between the XRCC1 Arg/Arg and Gln/Gln variants and the risk of colorectal cancer (OR = 1.28; 95% CI 1.00-1.84 and OR = 1.13; 95% CI 0.85-2.34, respectively). Gene-gene interaction between the XRCC1 Arg/Arg and XRCC3 Met/Met homozygous variants slightly increased the risk (OR = 10.50; 95% CI 5.67-14.79). Both polymorphisms were not associated with colorectal cancer progression.     

DNA repair gene XRCC3 Thr241Met polymorphism and hepatocellular carcinoma risk

The DNA repair genes have been indicated as candidates in the risk of hepatocellular carcinoma (HCC). Published data on the association between X-ray repair cross-complementing group 3 (XRCC3), a critical member of the DNA repair genes, and HCC risk were contradictory. The aim of this meta-analysis was to assess the effect of XRCC3 Thr241Met polymorphism on HCC risk by pooling available data from published case–control studies. We calculated the pooled odds ratio (OR) with the corresponding 95 % confidence interval (95 % CI) to estimate the effect. Based on the inclusion criteria, six individual studies with 2,288 cases and 3,170 controls were included into our study. Overall, significant association between the XRCC3 Thr241Met variant and HCC risk was observed under the following contrast models (OR_{Met vs. Thr}?=?1.68, 95 %CI 1.08–2.62; OR_{MetMet vs. ThrThr}?=?5.54, 95 %CI 3.09–9.94; OR_{MetMet vs. ThrThr?+?ThrMet}?=?5.70, 95 % CI 4.24–7.64). Besides, the pooled ORs indicated that the XRCC3 Thr241Met polymorphism exerted risk effect on the HCC pathogenesis among Asians. Additionally, when stratifying by the status of smoking and hepatitis B virus infection, the XRCC3 Thr241Met variant was significantly associated with HCC risk among the HBsAg (+) individuals but not the HBsAg (?) individuals, smokers, and non-smokers. The present meta-analysis suggests that the XRCC3 Thr241Met polymorphism is an independent risk factor for HCC, particularly among Asians and the HBsAg (+) individuals.     

No association between XRCC1 and XRCC3 gene polymorphisms and breast cancer risk: Iowa Women's Health Study

BACKGROUND: Genetic variation in DNA repair may contribute to differences in the susceptibility of several cancers. We evaluated two polymorphisms in the base excision repair pathway (BER) (XRCC1; Arg194Trp and Arg399Gln) and one polymorphism in the double strand DNA repair pathway (XRCC3; Thr241Met) for their association with breast cancer risk. METHODS: The association was analyzed in a nested case control study of 460 breast cancer cases and 324 cancer-free controls within the Iowa Women's Health Cohort. DNA was obtained from blood samples or paraffin embedded tissues (PET) and all samples were genotyped by one of three genotyping platforms-PCR-RFLP, PCR-INVADER, or Sequenom. RESULTS: None of the three polymorphisms studied were significantly associated with breast cancer risk (XRCC1: Arg194Trp (OR=1.21, 95% CI: 0.78-1.88); Arg399Gln (OR=1.20, 95% CI: 0.80-1.79); XRCC3: Thr241Met (OR=1.04, 95% CI: 0.76-1.41). CONCLUSIONS: These results suggest that independently these polymorphisms of XRCC1 and XRCC3 genes do not contribute significantly to the genetic susceptibility of breast cancer.     

The XRCC3 Thr241Met Polymorphism Influences Glioma Risk - A Meta-analysis

Background: Findings from previous published studies regarding the association of the XRCC3 Thr241Metpolymorphism with glioma susceptibility have often been conflicting. Therefore, a meta-analysis including allavailable publications was carried out to make a more precise estimation of the potential relationship. Methods:By searching the electronic databases of Pubmed and Embase (up to April 1st, 2013), a total of nine case-controlstudies with 3,752 cases and 4,849 controls could be identified for inclusion in the current meta-analysis. Oddsratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the association. Results:This meta-analysis showed the XRCC3 Thr241Met polymorphism to be significantly associated with decreasedglioma risk in the allelic model (Met allele vs. Thr allele: OR= 0.708, 95%CI= 0.631-0.795). Moreover, we alsoobserved a statistically significant association between the XRCC3 Thr241Met polymorphism and reducedglioma risk in analyses stratified by ethnicity (Asian) and source of controls (hospital based) in the allelic model.Conclusions: Current evidence suggests that the XRCC3 Thr241Met polymorphism may be a risk factor forglioma development, especially in Asians.     

XRCC3 Thr241Met polymorphism with lung cancer and bladder cancer: A meta‐analysis

Several studies have investigated the associations between X‐ray repair cross‐complementing group 3 (XRCC3) Thr241Met polymorphism and the susceptibility to lung cancer and bladder cancer, but results have been inconclusive. In order to derive a more precise estimation of the relationship, a meta‐analysis was performed. A total of 22 case control studies, including 2976 cases and 4495 controls for lung cancer, and 3445 cases and 4599 controls for bladder cancer, met the inclusion criteria and were selected. Overall, there was no evidence showing a significant association between XRCC3 Thr241Met polymorphism and lung cancer risk. Furthermore, the results for bladder cancer showed that significant decreased risk was found for the additive model (odds ratio [OR] = 0.959, 95% confidence interval [CI], 0.924–0.996) and dominant model (OR = 0.982, 95% CI, 0.963–1.000) but not for the recessive model (OR = 0.958, 95% CI, 0.905–1.014). In summary, our meta‐analysis indicates that XRCC3 Thr241Met polymorphism may be weakly associated with the risk of bladder cancer. (Cancer Sci 2010)     

Polymorphisms of DNA repair genes and risk of glioma

DNA repair genes play a major role in maintaining genomic stability through different repair pathways that are mediated by cell cycle control genes such as p53. We found previously that glioma patients were susceptible to gamma-ray-induced chromosomal breaks, which may be influenced by genetic variation in genes involved in DNA strand breaks, such as XRCC1 in single-strand break repair, XRCC3 and RAD51 in homologous recombination repair, and XRCC7 in nonhomologous end joining double-strand break repair. Therefore, we tested the hypothesis that genetic polymorphisms in XRCC1, XRCC3, RAD51, XRCC7, and p53 were associated with risk of glioma in 309 patients with newly diagnosed glioma and 342 cancer-free control participants frequency matched on age (+/- 5 years), sex, and self-reported ethnicity. We did not find any statistically significant differences in the distributions of XRCC1 Arg399Gln, XRCC3 Thr241Met, RAD51 G135C, and P53 Arg72Pro polymorphisms between the cases and the controls. However, the XRCC7 G6721T variant T allele and TT genotype were more common in the cases (0.668 and 43.4%, respectively) than in the controls (0.613 and 38.9%, respectively), and the differences were statistically significant (P = 0.045 and 0.040, respectively). The adjusted odds ratios were 1.78 (95% confidence interval, 1.08-2.94) and 1.86 (95% confidence interval, 1.12-3.09) for the GT heterozygotes and TT homozygotes, respectively. The combined T variant genotype (GT+TT) was associated with a 1.82-fold increased risk of glioma (95% confidence interval, 1.13-2.93). These results suggest that the T allele may be a risk allele, and this XRCC7 polymorphism may be a marker for the susceptibility to glioma. Larger studies are needed to confirm our findings and unravel the underlying mechanisms.     

Genetic Variations of RAD51 and XRCC2 Genes Increase the Risk of Colorectal Cancer in Bangladeshi Population

Objectives: In case of Bangladeshi population, no report is observed till now showing the genetic variations of RAD51 (rs1801320) and XRCC2 (rs3218536) genes polymorphism having association with colorectal cancer risk. For this reason the aim of this study is to ascertain their interrelation with colorectal cancer occurrence in Bangladeshi population. Materials and Methods: A case control study was conducted where 200 colorectal cancer patients and 200 healthy volunteers were figured for this research using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Results: Here, in case of RAD51 (rs1801320), G/C heterozygous genotype was found significant (p=0.037; OR=1.64; 95% CI=1.03 to 2.6). On the other hand, G/G genotype was not found statistically significant (p=0.423; OR=1.61; 95% CI=0.49 to 5.22) and significance was observed for GC+GG (p=0.030; OR=1.63; 95% CI=1.05 to 2.55). In case of XRCC2 (rs3218536), C/T heterozygous genotype was remarked statistically significant (p=0.033; OR=1.60; 95% CI=1.04 to 2.46). The T/T genotype was not recorded statistically significant (p=0.237; OR=1.65; 95% CI=0.72 to 3.76) but significance found for CT+TT (p=0.027; OR=1.61; 95% CI=1.05 to 2.45). Moreover, it is found that the risk factor of developing CRC is observed in G/C, C/T heterozygote and GC+GG, CT+TT (heterozygote+ mutant) in RAD51 (rs1801320) and XRCC2 (rs3218536) respectively although no significance is observed in case of G/G and T/T mutant. Conclusions: So, the association of RAD51 (rs1801320) and XRCC2 (rs3218536) genes polymorphism with colorectal cancer risk is observed in Bangladeshi population.