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

Chai, Fang; Liang, Yan; Chen, Li; Zhang, Fan; Jiang, Jun

doi:10.12659/msm.894637

Cited by 13 publications

(12 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At the meta-analytical level, Thr241Met polymorphism was related to increased risk of breast cancer when all investigations were grouped together. [20,21,22] That was in accordance with the results from the current work, where XRCC3 241Met was associated with increased risk for breast cancer, posing a 3.21 fold upraised risk on its carriers.…”

Section: Discussionsupporting

confidence: 92%

Impact of DNA Repair Genes Polymorphisms on Incidence and Prognosis of Breast Cancer in an Egyptian Cohort

Zaher¹,

Hemida²,

Al-Naggar³

2017

JCRT

View full text Add to dashboard Cite

Background: Sporadic breast cancer might be caused by low-penetrance genes, including genes constituting the DNA repair pathways. Defective DNA repair is a common imprint of cancer that promotes the accretion of DNA errors and genomic instability. The clustering of damage in DNA may stimulate breast carcinogenesis. Aims: The goal of the study is to evaluate the role of single nucleotide polymorphisms in DNA repair genes XRCC1 Arg399Gln, XPD Lys751Gln, RAD51 G135C and XRCC3 Thr241Met as genetic indicators of susceptibility to breast cancer and to evaluate their role in treatment outcome. Methodology: The study included 248 females diagnosed with primary breast cancer and 232 normal healthy females. Patients were clinically followed up for 5 years after completing chemotherapy. Genomic DNA was isolated and the four polymorphisms under investigation were assessed by PCR-RFLP technique. Findings: XRCC1 399Gln, XPD 751Gln and XRCC3 241Met alleles were significantly associated with breast cancer risk (OR = 2.63, 2.17 and 3.21; respectively), with carriers having lower disease free survival (DSF). When grouping patients based on the number of affected genotypes they carry, DFS decreased as the number of affected genotypes increased (P accum <0.001), patients carrying three (HR=4.74, p<0.001) or two (HR=3.35, p=0.005) affected genotypes had significantly worse DFS compared with those carrying zero (reference) or one (HR=1.37, p=0.093) affected genotype. RAD51 5'UTR G135C polymorphism was not associated with breast cancer risk (p=0.932) or with DFS. Conclusion: XRCC1 Arg399Gln, XPD Lys751Gln and XRCC3 Thr241Met polymorphisms may take a significant part in sporadic breast cancer as risk factors and in prognosis, where patients carrying XRCC1 Arg/Arg, XPD Lys/Lys and XRCC3 Thr/Thr genotypes had significantly diminished risk for breast cancer and higher DFS. DFS decreased as the number of affected genotypes increased. But RAD51 5'UTR G135C polymorphism did not associate with either risk or prognosis of breast cancer.

show abstract

Section: Discussionsupporting

confidence: 92%

Impact of DNA Repair Genes Polymorphisms on Incidence and Prognosis of Breast Cancer in an Egyptian Cohort

Zaher¹,

Hemida²,

Al-Naggar³

2017

JCRT

View full text Add to dashboard Cite

show abstract

“…We conducted the present systematic review protocol according to the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) [14]. We also registered the study protocol on the international prospective register of systematic review (PROSPERO) network.…”

Section: Methodsmentioning

confidence: 99%

“…Association between the mentioned SNP and breast cancer risk were analyzed by pooling odds ratio (ORs) with 95% confidence interval (CIs) in three models including dominant (TM + MM vs.TT), recessive (MM vs. TM + TT), and homozygote (MM vs.TT) models using STATA metan module. Z test was applied to assess the significance of the ORs, The heterogeneity between included publications was evaluated using I 2 parameter as described previously [14] where the higher values indicate higher level of heterogeneity. Furthermore, we checked heterogeneity by the chi-square-based Q-test (Heterogeneity was considered statistically significant if p < 0.05) (Egger et al, 1997).…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2019

View full text Add to dashboard Cite

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. Electronic supplementary material The online version of this article (10.1186/s12881-019-0809-8) contains supplementary material, which is available to authorized users.

show abstract

“…In the case of Xrcc3, rs861539 (c.722C>T; 241 Thr/Met) in exon 8 is the most frequently tested SNP with respect to cancer risk. The risk of BrC among carriers of the 241 Met-containg genotypes was found to be increased compared to wild-type carriers by some 6-10% under various genetic models [29][30][31]. Nevertheless, recent smaller studies conducted in Polish BrC population failed to provide evidence on any unambiguous effect with respect to BrC risk [32,33].…”

Section: Introductionmentioning

confidence: 96%

Rad51 paralogs and the risk of unselected breast cancer: A case-control study

2020

View full text Add to dashboard Cite

A case-control study was conducted in which we evaluated the association between genetic variability of DNA repair proteins belonging to the Rad51 family and breast cancer (BrC) risk. In the study, 132 female BrC cases and 189 healthy control females were genotyped for a total of 14 common single nucleotide polymorphisms (SNPs) within Rad51 and Xrcc3. Moreover, our previously reported Rad51C genetic data were involved to explore the nonlinear interactions among SNPs within the three genes and effect of such interactions on BrC risk. The rare rs5030789 genotype (-4601 AA) in Rad51 was found to significantly decrease the BrC risk (OR = 0.5, 95% CI: 0.3-1.0, p<0.05). An interaction between this SNP, rs2619679 and rs2928140 (both in Rad51), was found to result in a two three-locus genotypes-4719 AA/-4601 AA/ 2972 CG and-4719 AT/-4601 GA/ 2972 CC, both of which were found to increase the risk of BrC (OR = 8.4, 95% CI: 1.8-38.6, p<0.0001), instead. Furthermore, rare Rad51 rs1801320 (135 CC) and heterozygous Xrcc3 rs3212057 (10343 GA) genotypes were found to respectively increase (OR = 10.6, 95% CI: 1.9-198, p<0.02) and decrease (OR = 0.0, 95% CI: 0.0-NA, p<0.05) the risk of BrC. Associations between these SNPs and BrC risk were further supported by outcomes of employed machine learning analyses. In Xrcc3, the 4541 A/ 9685 A haplotype was found to be significantly associated with reduced BrC risk (OR = 0.5; 95% CI: 0.3-0.9; p<0.05). Concluding, our study indicates a complex role of SNPs within Rad51 (especially rs5030789) and Xrcc3 in BrC, although their significance with respect to the disease needs to be further clarified.

show abstract

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

Cited by 13 publications

References 30 publications

Impact of DNA Repair Genes Polymorphisms on Incidence and Prognosis of Breast Cancer in an Egyptian Cohort

Impact of DNA Repair Genes Polymorphisms on Incidence and Prognosis of Breast Cancer in an Egyptian Cohort

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

Rad51 paralogs and the risk of unselected breast cancer: A case-control study

Contact Info

Product

Resources

About