Many epidemiologic studies have investigated the association between x-ray repair cross-complementing group 1 gene (XRCC1) codon 399 polymorphism and lung cancer risk, but the results were inconsistent. We performed a meta-analysis of 46 studies on XRCC1 codon 399 polymorphism and lung cancer risk published before June 2013. In general population, the M allele and MM genotype were associated with increased risk of lung cancer compared with C allele and CC genotype, and the ORs were 1.06 (95% CI 1.01-1.12) and 1.19 (95% CI 1.05-1.34), respectively. When it was stratified according to Asian population, the association between XRCC1 codon 399 polymorphism and lung cancer risk was further strengthened. The ORs of comparison between M vs. C, MM vs. CC, and MM vs. CM + CC were 1.14 (95% CI 1.03-1.26), 1.41 (95% CI 1.11-1.78), and 1.38 (95% CI 1.12-1.71), respectively. The association between codon 399 polymorphism and lung cancer risk in nonsmoking Chinese women was stronger than any other subgroups. However, no associations were found in the Caucasian and African population. This meta-analysis has demonstrated that codon 399 polymorphism of XRCC1 gene might contribute to individual's susceptibility to lung cancer in Asian population, and especially in nonsmoking Chinese women. Future studies focused on interactions between combined genes and environmental risk factors are warranted.

Tumor necrosis factor alpha (TNF-α) has been suggested to play an important role in the development and liver cancer. TNF-α 238 G/A polymorphism was hypothesized to increase the risk of liver cancer, but findings from previous studies were controversial. To explore a more precise estimation of the relationship between TNF-α 238 G/A polymorphism and liver cancer, we performed a meta-analysis. PubMed, Embase, and China Biology Medicine databases were searched for all publications on this association through March 12, 2013. Odds ratios (ORs) with its 95% confidence intervals (CIs) were used to assess the strength of this association. Eleven studies with 1,406 liver cancer cases and 2,386 noncancer controls were included into this meta-analysis. Overall, there was a significant association between TNF-α 238 G/A polymorphism and increased risk of liver cancer under all three genetic models (A vs. G, OR 1.51, 95% CI 1.20-1.89, P < 0.001, I(2) = 37.7%; AG vs. GG, OR 1.49, 95% CI 1.01-2.21, P = 0.045, I(2) = 53.2%; AA/AG vs. GG, OR 1.76, 95% CI 1.35-2.30, P < 0.001, I(2) = 36.5%). The sensitivity analysis further strengthened the validity of the positive association. Subgroup analysis of nine studies from Asian countries showed that there was a significant association between TNF-α 238 G/A polymorphism and increased risk of liver cancer in Asians (A vs. G, OR 1.35, 95% CI 1.03-1.76, P = 0.027, I(2) = 40.2%; AA/AG vs. GG, OR 1.56, 95% CI 1.14-2.15, P = 0.006, I(2) = 41.9%). In conclusion, TNF-α 238 G/A polymorphism is significantly associated with increased risk of liver cancer, especially in Asians.

X-ray repair cross-complementing protein 3 (XRCC3) is an essential gene involved in the double-strand break repair pathway. Published evidence has shown controversial results about the relationship between XRCC3 Thr241Met polymorphism and clinical outcomes of non-small cell lung cancer (NSCLC) patients receiving platinum-based chemotherapy.

The Val158Met polymorphism of the COMT gene has been implicated in susceptibility to uterine leiomyoma (ULM), but the reported results were inconclusive. The aim of the study was to evaluate the Val158Met polymorphism of the COMT gene and the risk of ULM by meta-analysis. A comprehensive electronic search for relevant articles was conducted in Pubmed, Embase, CNKI, Wanfang, and Weipu databases. Statistical analysis was performed by using the Revman4.2 software and Stata10.0 software. A total of 7 articles including 12 case-control studies were identified in this meta-analysis. The results showed that the polymorphism was associated with decreased risk of ULM (Met/Met+Val/Met vs. Met/Met: OR=0.84, 95% CI=0.70-0.99, Z=2.07, p=0.04). In the subgroup analyses by ethnicity, significant decreased risk was found among the black populations (OR=0.68, 95% CI=0.48-0.97, Z=2.15, p=0.03). The current meta-analysis suggested that the Val158Met polymorphism in the COMT gene was associated with decreased risk of ULM, especially in the black population. Future studies are needed to validate our conclusions.

Previous studies have focused on the association of miR-34 family members with carcinogenesis of many cancers, including hepatocellular carcinoma (HCC). It has been suggested that miR-34b/c polymorphism (rs4938723) is associated with susceptibility to HCC. In the present study, we performed a meta-analysis to systematically summarize the possible association between rs4938723 and the risk for HCC.

Genome-wide association studies have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesised that SNPs previously associated with other cancers may additionally be associated with colorectal cancer. In a large-scale study, we examined 171 SNPs previously associated with 18 different cancers for their associations with colorectal cancer.

In the present study we conducted a systematic review and meta-analysis of published data to quantify the impact of the DPYD IVS14+1G>A and 2846A>T variants on the risk of fluoropyrimidine-related toxicities and to determine sensitivity and specificity testing for DPYD variants.

Epithelial-mesenchymal transition (EMT) plays a crucial role in the progression and aggressiveness of colorectal carcinoma. E-cadherin is the best-characterized molecular marker of EMT, but its prognostic significance for patients with CRC remains inconclusive.

Many studies proposed that cytochrome P450 1A1 (CYP1A1) MspI polymorphism may be associated with endometrial cancer risk, but the findings from previous studies reported conflicting results. A meta-analysis of all relevant studies was performed to get a comprehensive assessment of the association between CYP1A1 MspI polymorphism and endometrial cancer risk. Eligible studies were searched in PubMed and China National Knowledge Infrastructure databases. The pooled odds ratios (ORs) with the corresponding 95 % confidence intervals (95 % CIs) were calculated to evaluate the association. Twelve studies with a total of 2,111 cases and 2,894 controls were finally included into the meta-analysis. Overall, meta-analysis of a total of 12 studies showed that there was no obvious association between CYP1A1 MspI polymorphism and endometrial cancer risk (ORC vs. T = 0.97, 95 % CI 0.77-1.22, P OR = 0.808; ORCC vs. TT = 1.00, 95 % CI 0.57-1.76, P OR = 0.994; ORCC vs. TT/TC = 0.88, 95 % CI 0.65-1.20, P OR = 0.425; ORCC/TC vs. TT = 0.98, 95 % CI 0.74-1.29, P OR = 0.861). Subgroup analyses by ethnicity further showed that there was no obvious association between CYP1A1 MspI polymorphism and endometrial cancer risk in both Caucasians and Asians. There was no obvious risk of publication bias. Therefore, the meta-analysis suggests that CYP1A1 MspI polymorphism is not associated with endometrial cancer risk.

Numerous studies have investigated the association between three polymorphisms (Lys939Gln, Ala499Val and PAT-/+) of Xeroderma pigmentosum group C (XPC) gene and bladder cancer susceptibility; however, the findings are inconclusive. In order to acquire a more precise estimation of the relationship, we performed a meta-analysis based on 10 studies including 3,934 cases and 4,269 controls for Lys939Gln, five studies including 2,113 cases and 2,249 controls for Ala499Val, and seven studies including 2,834 cases and 3,048 controls for PAT-/+ polymorphism. We searched publications from EMBASE, MEDLINE, and Chinese Biomedical. We calculated pooled odds ratio (OR) and 95% confidence interval (CI) by using either fixed-effects or random-effects model according to the between-study heterogeneity. We found that all studied polymorphisms were individually associated with increased overall cancer risks, as shown by ORs (95% CIs) below: the Lys939Gln (Gln/Gln vs. Lys/Lys: OR = 1.39, 95% CI = 1.08-1.79; recessive model: OR = 1.42, 95% CI = 1.11-1.83; and allele comparing: OR = 1.12, 95% CI = 1.003-1.24), the Ala499Val (Val/Val vs. Ala/Ala: OR = 1.82, 95% CI = 1.19-2.79; recessive model: OR = 1.70, 95% CI = 1.18-2.46; and allele comparing: OR = 1.23, 95% CI = 1.01-1.50), and the PAT-/+ (+/+ vs. -/-: OR = 1.36, 95% CI = 1.03-1.79 and recessive model: OR = 1.34, 95% CI = 1.06-1.70). Furthermore, stratification analyses demonstrated an increased risk for Asian populations as to the Lys939Gln and PAT-/+ whereas for Caucasian populations as to the Ala499Val polymorphism in the homozygous and recessive models. Despite some limitations, this meta-analysis suggests that XPC polymorphisms are associated with bladder cancer risk, but this association warrants further validation in well-designed studies with large sample sizes.

Genetic polymorphism of X-ray repair cross-complementing group 3 (XRCC3) Thr241Met has been implicated to alter the risk of glioma, but the results are controversial. Medline, PubMed, Embase, and Cochrane Library databases were independently searched by two investigators up to 13 July 2013. Summary odds ratios (OR) and 95% confidence interval (CI) for Thr241Met polymorphism and prostate cancer were calculated. Statistical analysis was performed with the software program Stata 12.0. A total of 10 independent studies, including 4,136 cases and 5,233 controls, were identified. Our analysis suggested that Thr241Met was not associated with glioma risk in overall population. In the subgroup analysis, we detected no significant association between Thr241Met polymorphism and glioma risk in different descent populations. Subgroup analysis was held by source of controls, significant association was found between this polymorphism and glioma risk for population-based studies (homozygote model: OR = 1.747, 95% CI = 1.123-2.717, Ph = 0.059, I(2) = 59.7%; recessive model, OR = 1.455, 95% CI = 1.179-1.795, Ph = 0.111, I(2) = 50.1%; allele model, OR = 1.258, 95% CI = 1.010-1.566, Ph = 0.011, I(2) = 72.9%). This meta-analysis showed the evidence that XRCC3 Thr241Met polymorphism was associated with a low risk of glioma development.

Vascular endothelial growth factor (VEGF), the most important regulator of angiogenesis and vascular permeability, is involved in various steps of carcinogenesis. The +936C/T polymorphism of the VEGF gene has been reported to affect the VEGF protein level and to be related to the susceptibility of cancer. However, the results of published studies, as well as the subsequent meta-analyses, remain contradictory. We investigated the association between VEGF +936C/T polymorphism and cancer risk in the Asian population. Twenty-one papers were selected from the PubMed database after a systematic search. Statistics on the frequencies of CC, CT, and TT genotypes of the VEGF +936C/T gene were collected from 8298 cases and 8053 controls. No significant associations between the VEGF +936C/T polymorphism and cancer risk were found for alleles T vs C [odd ratio (OR) = 0.99, 95% confidence interval (95%CI) = 0.93-1.05], TT vs CT/CC (OR = 1.05, 95%CI = 0.88-1.26), CC vs CT/TT (OR = 1.02, 95%CI = 0.96-1.10), and TT vs CC (OR = 1.05, 95%CI = 0.88-1.25). No significant associations were detected in the subgroup analysis by cancer type either. The VEGF +936C/T polymorphism is not associated with risk of overall cancer among Asians.

It has been demonstrated that MDM2 is a well-established negative regulator of the p53 protein and might be associated with a significantly earlier age of onset of several tumors, including colorectal cancer (CRC). In recent years, a T to G substitution (SNP309) in the promoter of MDM2 has been extensively studied as a potential CRC risk factor; however, the results are inconsistent. To derive a more precise estimation of association between MDM2 SNP309 polymorphism and CRC risk, we conducted a meta-analysis of 11 studies with 4,050 CRC cases and 3,688 controls. For MDM2 SNP309 polymorphism, no obvious associations were found for all genetic models when all studies were pooled into the meta-analysis. In the subgroup analyses by ethnicity, source of controls, and Hardy-Weinberg equilibrium (HWE) in controls, a significantly increased risk was observed among Asians (heterozygous model: odds ratio (OR) = 1.21, 95% confidence interval (CI) = 1.06-1.39, P = 0.005), population-based studies (heterozygous model: OR = 1.17, 95% CI = 1.02-1.34, P = 0.027), and among studies without the HWE (recessive model: OR = 1.42, 95% CI = 1.03-1.94, P = 0.030). When excluding three studies deviated from HWE, the significant results were also observed for heterozygous model in overall population (OR = 1.16, 95% CI = 1.02-1.31, P = 0.020). No publication bias was found in the present study. In conclusion, this meta-analysis suggests that MDM2 SNP309 polymorphism was associated with CRC susceptibility, especially among Asians. Further research is needed to assess possible gene-gene or gene-environment-lifestyle interactions on CRC.

The oxoguanine DNA glycosylase (OGG1) Ser326Cys polymorphism has been implicated in susceptibility to esophageal cancer. Several studies investigated the association of this polymorphism with esophageal cancer in different populations. However, the results were contradictory. A meta-analysis was conducted to assess the association between the OGG1 Ser326Cys polymorphism and esophageal cancer susceptibility.

Chromosome 3q26-29 is a critical region of genomic amplification in lung squamous cell carcinomas (SCC). Identification of candidate drivers in this region could help uncover new mechanisms in the pathogenesis and potentially new targets in SCC of the lung.

Vascular endothelial growth factor (VEGF) is considered as a prime mediator of angiogenesis and has been implicated in carcinogenesis and metastasis. Various studies examined the relationship between VEGF overexpression with the clinical outcome in patients with osteosarcoma but yielded conflicting results. Electronic databases updated to April 2013 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between VEGF overexpression and survival of patients with osteosarcoma. Survival data were aggregated and quantitatively analyzed. We performed a meta-analysis of eight studies that evaluated the correlation between VEGF overexpression and survival in patients with osteosarcoma. Combined hazard ratios suggested that VEGF overexpression had an unfavorable impact on overall survival (hazard ratio (HR) = 1.75, 95% confidence interval (CI): 1.21-2.28) in patients with osteosarcoma for overall populations, 2.37 (1.35-3.39) in Asian studies but not in non-Asian studies (HR = 1.51, 95% CI: 0.89-2.14). No significant heterogeneity was observed among all studies. VEGF overexpression indicates a poor prognosis for patients with osteosarcoma. However, the prognostic value of VEGF on survival in osteosarcoma patients still needs further large-scale prospective trials to be clarified.

Abstract To date, many studies on the association between methionine synthase (MTR) A2756G and childhood acute lymphoblastic leukemia (ALL) have provided either controversial or inconclusive results. To clarify the effect of MTR A2756G on the risk of childhood acute lymphoblastic leukemia, a meta-analysis of all relevant studies was performed. The fixed effects model showed that the 2756A allele was associated with a decreased risk of childhood ALL compared with the G allele (ORA vs. G = 0.872; 95% CI 0.782-0.974; p = 0.015, I(2) = 46.9%). Additionally, when comparing subjects with ALL and controls with AA vs. AG or AA vs. AG + GG (dominant model), significant differences were found in the fixed effects model (ORAA vs. AG = 0.869; 95% CI 0.760-0.994; p = 0.040, I(2) = 26.4%; ORAA vs. AG+ GG = 0.858; 95% CI 0.754-0.976; p = 0.020, I(2) = 39.6%). In a subgroup analysis in a population with the same background, individuals with the AA genotype had a reduced risk of developing ALL compared to individuals with the AG genotype. In conclusion, our study provides evidence suggesting that MTR A2756G is associated with a reduced risk of developing childhood ALL.

Tumor necrosis factor β (TNF-β) 252 A/G polymorphism has been implicated to be associated with risk of gastric cancer, but previous studies showed inconsistent and inconclusive results. Therefore, we performed a meta-analysis to assess the association between TNF-β 252 A/G polymorphism and gastric cancer risk. Relevant studies were searched from PubMed database. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to evaluate the strength of the associations between TNF-β 252 A/G polymorphism and gastric cancer risk. Overall, 11 individual case-control studies with 2,270 cases and 4,404 controls were included in the final meta-analysis. Meta-analysis of total 11 studies showed that TNF-β 252 A/G polymorphism was associated with the risk of gastric cancer (G vs. A: OR = 1.10, 95% CI 1.02-1.19, P = 0.015; GG/AG vs. AA: OR = 1.21, 95% CI 1.00-1.47, P = 0.049). Subgroup analysis by ethnicity showed that TNF-β 252 A/G polymorphism was only associated with the risk of gastric cancer in Asians, but not Caucasians. The findings from the current meta-analysis suggest that TNF-β 252 A/G polymorphism is associated with the risk of gastric cancer, especially in Asians.

Previous studies proposed that isocitrate dehydrogenase 1 (IDH1) mutation was associated with improved survival in patients with glioblastoma, but those studies reported varying estimates and yielded inconclusive results. The purpose of the present study was to determine the effect of IDH1 mutation on the prognosis of patients with glioblastoma by performing a meta-analysis. Pubmed and Embase databases were searched for eligible studies. Studies reporting overall survival by IDH1 mutation in patients with glioblastoma were considered potentially eligible for the meta-analysis. For the quantitative aggregation of the survival results, the IDH mutation effect was measured by the pooled hazard ratio (HR) with its 95% confidence interval (95%CI). Nine studies with a total of 1,669 patients with glioblastoma were finally included into this meta-analysis. Overall, the IDH1 mutation was associated with improved survival in patients with glioblastoma (random effects model HR = 0.45, 95%CI 0.29-0.69, P < 0.001). Sensitivity analysis further showed that the pooled estimates were stable in this meta-analysis. Therefore, the findings from this meta-analysis suggest that IDH1 mutation is associated with improved overall survival in patients with glioblastoma.

Previous studies on the association of Vitamin D receptor (VDR) TaqI gene polymorphism with breast carcinogenesis have yielded inconsistent and inconclusive findings. The current meta-analysis was performed to provide a more precise assessment on the role of VDR TaqI polymorphism in breast cancer risk. 20 eligible case-control studies involving 9,055 cases and 10,516 controls were identified after a comprehensive literature search of the PubMed, Embase, Web of Science, and Wanfang databases. The pooled odds ratio (OR) with corresponding 95% confidence interval (95% CI) was calculated. Stratified analyses by ethnicity and study quality were conducted for further estimation. All statistical analyses were conducted by use of STATA (STATA Corporation, College Station, TX, Version 11.0). The overall ORs showed that the variant t allele and tt genotype were related to an increased risk of breast cancer (OR(t vs. T) = 1.05, 95% CI 1.01-1.10, P(OR) = 0.025; OR(tt vs. TT) = 1.12, 95% CI 1.03-1.23, P(OR) = 0.011; OR(tt vs. Tt + TT) = 1.10, 95% CI 1.01-1.20, P(OR) = 0.023). Stratified analyses of studies in Caucasians and with high-quality further confirmed the results. However, no significant relationship was observed among Asians. This meta-analysis suggests that the VDR TaqI polymorphism confers risk effect on the breast cancer development, particularly in Caucasians.