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.     

RAD51 135G>C polymorphism contributes to breast cancer susceptibility: a meta-analysis involving 26,444 subjects

RAD51 plays a key role in homologous recombination repair of double-stranded DNA breaks which may cause chromosomal breaks and genomic instability. We performed a meta-analysis of 9 epidemiological studies involving 13,241 cases and 13,203 controls that examined the association between RAD51 135G>C polymorphism and breast cancer. No significant association of RAD51 135G>C polymorphism with breast cancer was found in overall and European populations. However, after the studies which did not fulfill Hardy–Weinberg equilibrium were excluded, we observed an overall significant increased breast cancer risk (for the recessive model CC vs. GG/CG: OR = 1.35, 95% CI = 1.05–1.74, P _{heterogeneity} = 0.06). In summary, our meta-analysis suggested the RAD51 135G>C polymorphism may contribute to breast cancer susceptibility.     

RAD51 135G>C does not modify breast cancer risk in non-BRCA1/2 mutation carriers: evidence from a meta-analysis of 12 studies

A single-nucleotide polymorphism (SNP) in the 5′-untranslated region (UTR) of RAD51, 135G>C (rs1801320), was reported to be associated with an increased risk of breast cancer among BRCA2 as well as BRCA1 carriers. A few studies have also investigated the genetic contribution of RAD51 135G>C to the risk of sporadic breast cancers or breast cancer in non-BRCA1/2 carriers, though the results are yet controversial and inconclusive. We, in this study, performed a more precise estimation of the relationship between 135G>C and breast cancer among non-BRCA1/2 mutation carriers by meta-analyzing the currently available evidence from the literature. A total of 12 studies involving 7,065 cases and 6,981 controls were identified. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. When all the studies were pooled into the meta-analysis, there was no evidence for a significant association between 135G>C and breast cancer risk in non-BRCA1/2 mutation carriers (for CC vs. GG: OR = 0.995, 95%CI: 0.741–1.336; for GC vs. GG: OR = 0.959, 95%CI: 0.869–1.057; for dominant model: OR = 0.988, 95%CI: 0.902–1.082; and for recessive model: OR = 1.037, 95%CI: 0.782–1.376). We also performed subgroup analysis by ethnicity (Caucasian) as well as did analysis using the studies fulfilling Hardy–Weinberg equilibrium, and the results did not change. In summary, the present meta-analysis suggests that the RAD51 135G>C does not modify breast cancer risk in non-BRCA1/2 mutation carriers.     

RAD51 135G>C and TP53 Arg72Pro polymorphisms and susceptibility to breast cancer in Serbian women

Breast cancer is a complex disease with both genetic and environmental factors involved in its etiology. An important role of polymorphisms in genes involved in DNA repair has been reported related to breast cancer risk. We conducted a case–control study in order to investigate the association of RAD51 135G>C and TP53 Arg72Pro polymorphisms with breast cancer in Serbian women.48 BRCA negative women with breast cancer and family history of breast/ovarian cancer (hereditary group), 107 women with breast cancer but without family history of the disease (sporadic group) and 114 healthy women without a history of the disease (control group) were included. Restriction fragment length polymorphism was used for genotyping. Genotype and allelic frequencies, the odds ratio (OR) and the 95 % confidence interval (CI) were calculated as an estimate of relative risk. The Hardy–Weinberg equilibrium was tested using χ² test. Significance was considered for p < 0.05. RAD51 135G>C showed statistically significant association of CC genotype and increased breast cancer risk (OR 10.28, 95 % CI 1.12–94.5) in hereditary group of patients compared to the control group. Regarding the TP53 Arg72Pro, we showed statistical significance for ProPro + ProArg comparing to ArgArg (OR 2.34, 95 %, CI 1.17–4.70) in hereditary compared to sporadic group. RAD51 135G>C contributes to hereditary breast cancer in Serbian population, with CC genotype as a risk factor. We also found that carriers of Pro allele of TP53 codon 72 is related to hereditary cancer comparing to sporadic one, which indicates it as a potential risk factor for hereditary form of disease.     

Survivin rs9904341 (G>C) polymorphism contributes to cancer risk: an updated meta-analysis of 26 studies

Survivin, a member of the inhibitor of apoptosis protein family, encoded by BIRC5, is involved in the regulation of apoptosis and in cell cycle control. Emerging evidences indicate that polymorphism in BIRC5 promoter (rs9904341) is associated with cancer risk, but the results of individually published studies are inconclusive. Thus, an updated meta-analysis was performed. PubMed was searched for all eligible studies. Pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated to assess the association strength. Stratified analysis was performed by cancer type, source of control, genotyping method, and ethnicity. A number of 26 studies, including 6,041 cases and 7,567 controls were analyzed in this meta-analysis. Overall, significantly increased cancer risk was associated with survivin rs9904341 polymorphism when all studies were pooled (CC vs. GG: OR?=?1.36, 95 % CI?=?1.09–1.69; P _{heterogeneity}?<?0.001; CC vs GC/GG: OR?=?1.32, 95 % CI?=?1.11–1.57; P _{heterogeneity}?<?0.001). Stratified analysis by cancer type revealed that the survivin rs9904341 polymorphism may increase the risk of colorectal cancer, renal cell cancer, gastric cancer, and bladder cancer. Further subgroup analysis by ethnicity indicated that there was a statistically increased cancer risk in Asians but not Caucasians. In this updated meta-analysis of 26 studies, we conclude that the survivin rs9904341 polymorphism might contribute to risk of various cancers, especially in Asian populations.     

RAD51 G135C polymorphism is associated with breast cancer susceptibility: a meta-analysis involving 22,399 subjects

Several studies have investigated the associations between RAD51 G135C polymorphism and the susceptibility to breast 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 17 case control studies, including 12,153 cases and 10,245 controls, were selected. Overall, significant decreased risk was found for the additive model (OR = 0.995, 95% CI = 0.991–0.998) and dominant model (OR = 0.994, 95% CI = 0.991–0.998). In the subgroup analysis by ethnicity, statistically significantly decreased risk was found in Asians (additive model: OR = 0.977, 95% CI = 0.954–1.000 and dominant model: OR = 0.981, 95% CI = 0.963–1.000). In conclusion, this meta-analysis suggests that the RAD51 G135C polymorphism is a low-penetrant risk factor for developing breast cancer.     

Genetic 135G/C polymorphism of RAD51 gene and risk of cancer: a meta-analysis of 28,956 cases and 28,372 controls

The RAD51 gene is essential for the repair of damaged DNA related to tumor development. Although a number of genetic studies have attempted to link the 135G/C polymorphism of RAD51 gene to the risk of cancer, the results were inconclusive. The present study aimed at investigating the pooled association using the more comprehensive meta-analysis. The PubMed, EBSCO, and BIOSIS databases were searched to identify eligible studies which were published in English before March 2014. Data were extracted using standardized methods. The association was assessed by odds ratio (OR) with 95 % confidence interval (CI). Begg’s test was used to measure publication bias. Sensitivity analyses were also performed to assess the stability of the results. A total of 45 eligible studies with 28,956 patients and 28,372 controls were included in this meta-analysis. Overall, significant association was detected between 135G/C polymorphism and increased cancer risk (C allele vs. G allele: OR 1.23, 95 % CI 1.18–1.28; CC vs. GG: OR 2.41, 95 % CI 2.12–2.74; CC vs. CG: OR 3.86, 95 % CI 3.41–4.37; recessive model: OR 3.57, 95 % CI 3.19–4.00). In further stratified analysis, significantly elevated cancer risk was observed among Caucasians but not Asians. Subgroup analysis by different cancers also showed their significant associations in breast cancer, hematologic malignances, ovarian cancer, colorectal cancer and endometrial cancer, but not in head and neck cancer. Our results indicated that the RAD51 135G/C polymorphism was a candidate for susceptibility of cancer. The effect of the variants on the expression levels and the possible functional role of the variants in different cancers should be addressed in further studies.     

VEGF +405G/C (rs2010963) polymorphisms and digestive system cancer risk: a meta-analysis

Vascular endothelial growth factor (VEGF) polymorphisms, specifically +405G/C (rs2010963), reportedly influence the risk for various digestive cancers. However, the consequences of these polymorphisms remain controversial and ambiguous. Therefore, we performed a meta-analysis of 11 studies with VEGF +405G/C genotyping on 2,862 patients and 3,028 controls using the random effects model. We obtained a pooled odds ratio (OR) of 1.04 (95 % confidence interval (CI)?=?0.86–1.26) for the recessive genetic model, 1.07 (95 % CI?=?0.81–1.42) for the dominant genetic model, 1.09 (95 % CI?=?0.81–1.47) for the homozygote comparison, and 1.03 (95 % CI?=?0.83–1.27) for the heterozygote comparison. In the subgroup analysis of the recessive model, the OR was 1.20 (95 % CI?=?1.02–1.40) in colorectal cancer. These results show that VEGF +405G/C polymorphisms are unlikely to be a major determinant of susceptibility to digestive cancer. Furthermore, the subgroup analysis of recessive model indicates that VEGF +405G/C polymorphisms increase the risk for colorectal cancer.     

Genetic polymorphisms of XRCC3 Thr241Met (C18067T,rs861539) and bladder cancer risk: a meta-analysis of 18 research studies

The relationship of bladder cancer with the presence of X-ray cross-complementing group 3(XRCC3) genetic polymorphismThr241Met has been reported with inconsistent results. The objective of this study was to quantitatively evaluate the association between this polymorphism and bladder cancer susceptibility. A comprehensive research was conducted through PubMed, Medline, Embase, and Web of Science databases up to Aug. 20, 2013. Pooled odds ratio and 95 % confidence interval were calculated using a fixed or random effects model. Statistical analysis was performed with Stata 12.0 software. Of the 18 case–control studies selected for this meta-analysis, a total of 5,667 bladder cancer cases and 7,609 controls were included. The combined results based on all studies suggested that XRCC3 Thr241Met was associated with bladder cancer risk under homozygote and recessive models. When stratifying for ethnicity, significant association was found in Caucasians under homozygote and recessive models. This meta-analysis suggests that XRCC3 Thr241Met polymorphism is a risk factor for bladder cancer risk. However, further well-designed studies are required to confirm our findings.     

The RAD51 135 G>C polymorphism modifies breast cancer and ovarian cancer risk in Polish BRCA1 mutation carriers.

Breast and ovarian cancer penetrance in BRCA1 mutation carriers is estimated to be between 15% and 80% by age 70 years. At present, it is not possible to predict with any certainty who is most likely to develop disease or which age it will develop. Previous studies have tried to correlate the sites of BRCA1 mutations with disease risk; however, the results have not yielded any definitive association. An alternative explanation that could account for differences in the penetrance of BRCA1 mutations is the action of modifier genes. In this study, we have investigated the role of the RAD51_135_G>C polymorphism in breast and ovarian cancer case-control populations of Polish women who have been matched for BRCA1 mutation and year of birth. The results reveal that women who harbor the C allele have almost twice the reduction in breast and ovarian cancer risk compared with women who harbor only the G allele. These findings suggest that the effect of the RAD51 C allele is an important risk modifier for malignancies occurring on a background of BRCA1 mutations. In addition, we were able to show that the site of the BRCA1 mutation does not influence the effect of the RAD51 C allele, indicating that this polymorphism contributes to prevention of disease in BRCA1 carriers. In conclusion, the RAD51 C allele seems to protect against both breast and ovarian cancer in women harboring BRCA1 mutations.     

XRCC1 polymorphisms increase bladder cancer risk in Asians: a meta-analysis

X-ray cross complementing group 1 (XRCC1) polymorphisms and bladder cancer risk has been investigated for years, but the result in Asian population is till inconclusive. Thus, we performed this meta-analysis to determine the association of XRCC1 Arg194Trp, Arg280His, and Arg399Gln polymorphisms with bladder cancer risk in the Asian population. PubMed, EMBASE, and China National Knowledge Infrastructure were searched up to January 2013 to identify eligible studies. The association strength was measured with odd ratios (ORs) and 95 % confidence intervals (95 % CIs). A total of nine eligible studies, including 1,931 bladder cancer patients and 2,192 controls, were identified. Significant increased risk of bladder cancer was observed for Arg194Trp polymorphism (allele comparison OR?=?1.20, 95 % CI: 1.06–1.36, P_{heterogeneity}?=?0.11; dominant model OR?=?1.20, 95 % CI: 1.02–1.41, P_{heterogeneity}?=?0.37) and Arg280His polymorphism (heterozygote comparison OR?=?1.87, 95 % CI: 1.21–2.90, P_{heterogeneity}?=?0.01; dominant model OR?=?1.75, 95 % CI: 1.05–2.90, P_{heterogeneity}?=?0.01); however, Arg399Gln was not associated with susceptibility to bladder cancer. No evidence of publication bias was detected. Our meta-analysis results suggest that XRCC1 Arg194Trp and Arg280His polymorphisms are associated with significantly increased risk of bladder cancer in Asians.     

XRCC1 polymorphisms and pancreatic cancer: A meta-analysis

Objective:To assess the association between X-ray repair cross-complementating group 1 (XRCC1) polymorphisms and pancreatic cancer.Methods:We searched MEDLINE,Web of Science and HuGE Navigator at June 2010,and then quantitatively summarized associations of the XRCC1 polymorphisms with pancreatic cancer risk using meta-analysis.Results:Four studies with 1343 cases and 2302 controls were included.Our analysis found:at codon 194,the Trp allele did not decrease pancreatic cancer risk (Arg/Arg versus Trp/Trp:OR=0.97;95% CI:0.48-1.96;P=0.97;Arg/Arg versus Arg/Trp:OR=0.89;95% CI:0.70-1.13;P=0.55;Arg/Trp versus Trp/Trp:OR=1.06;95% CI:0.52-2.16;P=0.90);at codon 280,only a study showed a nonsignificant association between single nucleotide polymorphism with pancreatic cancer risk;at codon 399,the Gln allele also showed no signi?cant effect on pancreatic cancer compared to Arg allele (Arg/Arg versus Gln/Gln:OR=0.94;95% CI:0.74-1.18;Arg/Arg versus Arg/Gln:OR=0.97;95% CI:0.83-1.13;Arg/Gln versus Gln/Gln:OR=0.97;95% CI:0.77-1.22).The shape of the funnel plot and the Egger’s test did not detect any publication bias.Conclusion:There is no evidence that XRCC1 polymorphisms (Arg194Trp,Arg280His,and Arg399Gln) are associated with pancreatic cancer risk.     

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.     

DNA repair gene XRCC3 polymorphisms and bladder cancer risk: a meta-analysis

The X-ray repair cross-complementing group 3 (XRCC3) in homologous recombination repair (HRR) pathway plays a vital role in DNA double-strand break repair (DSBR). Variants in the XRCC3 gene might result in altered protein structure or function which may influence DSBR efficiency and lead to cancer. Numerous epidemiological studies have been conducted to evaluate the association between XRCC3 polymorphisms and bladder cancer risk. However, the results of these previous studies have been inconsistent. To derive a more precise estimation of the association, we performed a meta-analysis of all available studies relating XRCC3 polymorphisms and bladder cancer. All studies published up to April 2013 on the association between XRCC3 polymorphisms and bladder cancer risk were identified by searching electronic databases PubMed, EMBASE, and Chinese Biomedical Literature databases. The association between the XRCC3 polymorphisms and bladder cancer risk was assessed by odds ratios (ORs) together with their 95 % confidence intervals (CIs). A total of 16 case–control studies met the inclusion criteria and were selected. With respect to C18067T polymorphism, significant increased bladder cancer risk was found when all eligible studies were pooled into the meta-analysis (TT vs. CC: OR?=?1.174, 95%CI?=?1.033–1.335, P?=?0.014 and recessive model TT vs. TC?+?CC: OR?=?1.147, 95 %CI?=?1.020–1.290, P?=?0.022, respectively). The results were still significant after excluding the Hardy–Weinberg equilibrium violation studies (TT vs. CC: OR?=?1.178, 95 %CI?=?1.036–1.339, P?=?0.013 and recessive model TT vs. TC?+?CC: OR?=?1.144, 95 %CI?=?1.017–1.287, P?=?0.025, respectively). In subgroup analysis by ethnicity, significant elevated risk was found among Asians (dominant model TT?+?TC vs. CC: OR?=?1.285, 95 %CI?=?1.012–1.631). In the subgroup analyses according to smoking status, no significant association was detected in all genetic comparison models. With respect to A17893G and A4541G polymorphisms, no significant association with bladder cancer risk was observed in the overall and subgroup analyses. This meta-analysis suggests that the XRCC3 C18067T polymorphism was associated with increased bladder cancer risk especially among Asians. However, the XRCC3 A17893G and A4541G polymorphisms may not play important roles in bladder carcinogenesis. Further studies with larger sample sizes are needed to validate our finds.     

XRCC1 polymorphisms and cancer risk: a meta-analysis of 38 case-control studies.

Several potential functional polymorphisms (Arg194Trp, Arg280His, Arg399Gln) in the DNA base excision repair gene X-ray repair cross-complementing group 1 (XRCC1) have been implicated in cancer risk. Our meta-analysis on total of 11,957 cancer cases and 14,174 control subjects from 38 published case-control studies showed that the odds ratio (OR) for the variant genotypes (Trp/Trp + Arg/Trp) of the Arg194Trp polymorphism, compared with the wild-type homozygote (Arg/Arg), was 0.89 [95% confidence interval (95% CI), 0.81-0.98] for all tumor types without between-study heterogeneity. Similarly, the overall risk for the combined variant genotypes (His/His + Arg/His) of the Arg280His, compared with the wild homozygote (Arg/Arg), was 1.19 (95% CI, 1.00-1.42). However, there was no main effect in either recessive or dominant modeling for the Arg399Gln, and the variant Gln/Gln homozygote was not associated with overall cancer risk (OR, 1.01; 95% CI, 0.90-1.14). The analyses suggest that XRCC1 Arg194Trp, Arg280His polymorphisms may be biomarkers of cancer susceptibility and a single larger study with thousands of subjects and tissue-specific biochemical and biological characterization is warranted to further evaluate potential gene-to-gene and gene-to-environment interactions on XRCC1 polymorphisms and cancer risk.     

XRCC3 Thr241Met gene polymorphisms and lung cancer risk: a meta-analysis

Many studies have examined the association between the XRCC3 Thr241Met gene polymorphism and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The PubMed, Embase, Web of Science, and CNKI database was searched for case–control studies published up to July 2012. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated.Ultimately, 17 studies, comprising 4123 lung cancer cases and 5597 controls were included. Overall, for T allele carriers (TC + TT) versus the wild-type homozygotes (CC), the pooled OR was 0.95 (95% CI = 0.87-1.04 P = 0.228 for heterogeneity), for TT versus CC the pooled OR was 0.99 (95% CI = 0.86-1.15 P = 0.315 for heterogeneity). In the stratified analysis by ethnicity, histological types of lung cancer and smoking status, no any significantly risks were found for (C/T + T/T) vs C/C or T/T vs C/C. No publication bias was found by using the funnel plot and Egger''s test.Overall, there is no evidence showing a significant correlation between XRCC3 Thr241Met polymorphism and lung cancer risk stratified analysis by ethnicity, histology and smoking status.     

RAD51 135G>C polymorphism and breast cancer risk: a meta-analysis

Mutations in RAD51 gene are believed to be associated with elevated breast cancer risk. However, several case–control studies focusing on the association between RAD51 135G>C and breast cancer risk failed to achieve consensus. To clarify the effect of RAD51 135G>C polymorphism on breast cancer, a meta-analysis was performed. By searching PubMed and EMBASE, a total of 14 case–control studies, containing 12,183 cases and 10,183 controls, were included. The strength of association between RAD51 135G>C polymorphism and breast cancer risk was assessed by odds ratio (OR) with the corresponding 95% confidence interval (95% CI). When all the eligible studies were pooled into the meta-analysis, an elevated cancer risk was revealed in additive model (OR, 1.34; 95% CI, 1.01–1.78; P = 0.044) and recessive model (OR, 1.37; 95% CI, 1.03–1.82; P = 0.032). In subgroup analyses by ethnicity, BRCA1/2 mutation status, and family history, a significant association was found only among BRCA2 mutation carriers (additive model: OR, 4.92; 95% CI, 1.11–21.83; P = 0.036; recessive model: OR, 4.88; 95% CI, 1.10–21.67; P = 0.037). Sensitivity analysis did not perturb the results. In conclusion, this meta-analysis suggests that RAD51 variant 135C homozygote is associated with elevated breast cancer risk among BRCA2 mutation carriers.