Several epidemiologic studies have investigated the relationship between the polymorphisms of ERBB2 gene and breast cancer risk. However, the results are inconclusive. This meta-analysis aimed to assess the association between ERBB2 Ile655Val and Ala1170Pro polymorphisms and the susceptibility to breast cancer.

Though many studies were performed to assess the association between tumor necrosis factor-α (TNF-α) 238 G/A polymorphism and gastric cancer risk, there were no conclusive findings. A meta-analysis of previous published studies was performed to get a comprehensive assessment of the association between TNF-α 238 G/A polymorphisms and gastric cancer. The pooled odds ratios (ORs) and 95% confidence intervals (95 % CIs) were calculated to assess the association. Fifteen studies with a total of 7,795 participants were finally included into this meta-analysis. Overall, there was an obvious association between TNF-α 238 G/A polymorphism and increased risk of gastric cancer (A vs. G: OR = 1.32, 95% CI 1.02-1.72, P = 0.036; GA vs. GG: OR = 1.32, 95% CI 1.01-1.72, P = 0.042; and AA/GA vs. GG: OR = 1.34, 95% CI 1.02-1.76, P = 0.036). Subgroup analysis by ethnicity showed the statistically significant association between TNF-α 238 G/A polymorphism and gastric cancer was limited to Asian populations (A vs. G: OR = 1.59, 95% CI 1.29-1.97, P < 0.001; GA vs. GG: OR = 1.63, 95% CI 1.29-2.04, P < 0.001; and AA/GA vs. GG: OR = 1.64, 95%CI 1.31-2.05, P < 0.001), and there was no obvious association in Caucasians. In conclusion, TNF-α 238 G/A polymorphism is significantly associated with increased risk of gastric cancer, especially in Asians.

Many epidemiologic studies have investigated the association between vitamin D receptor (VDR) gene polymorphisms and breast cancer risk, but the results were inconsistent. We performed a meta-analysis of 31 studies on VDR polymorphisms, including FokI, BsmI, TaqI, and ApaI, and breast cancer risk published before May 2013. For FokI, the allele of f was found to be associated with increased risk of breast cancer compared with F (OR, 1.19; 95% CI, 1.03-1.36). Patients with ff genotype were at significantly higher risk of breast cancer compared with those with FF genotype (OR, 1.95; 95% CI, 1.66-2.29). In subgroup analysis by race, Fok1 polymorphism was significantly associated with breast cancer risk for Caucasian population (f vs. F: OR, 1.35; 95% CI, 1.14-1.59; ff vs. FF: OR, 2.18; 95% CI, 1.86-2.54; ff vs. FF + Ff: OR, 1.16; 95% CI, 1.03-1.30). For ApaI, aa genotype was associated with increased breast cancer risk in Asian population based on four studies (aa vs. Aa + AA, OR, 1.49; 95% CI, 1.12-1.98). No significant association was found between breast cancer risk and ApaI and TaqI polymorphism in different models and populations. Our updated meta-analysis showed that Fok1 polymorphism is associated with breast cancer risk both in general population and in Caucasian population. ApaI polymorphism might be associated with breast cancer risk in Asian population. Large well-designed epidemiological studies are necessary to clarify the risk identified in the current meta-analysis.

Previous studies published to evaluate the association between FAS A670G polymorphism and susceptibility to cervical cancer provided conflicting findings. A meta-analysis of published case-control studies was performed to get a comprehensive evidence for the possible association. We searched in PubMed and Wanfang databases for eligible studies published before February 10, 2013. The odds ratio (OR) with 95% confidence interval (95% CI) was used to evaluate the association. Ten studies with a total of 4,904 participants were finally included into the meta-analysis. Overall, there was no obvious association between FAS A670G polymorphism and susceptibility to cervical cancer under all four genetic models (G versus A: OR = 0.97, 95% CI 0.84-1.11, P = 0.64; GG versus AA: OR = 0.92, 95% CI 0.69-1.24, P = 0.60; GG/AG versus AA: OR = 0.99, 95% CI 0.77-1.26, P = 0.92; GG versus AA/AG: OR = 0.92; 95% CI 0.68-1.25, P = 0.59). Subgroup analyses by ethnicity further showed that there was no association between FAS A670G polymorphism and susceptibility to cervical cancer in both Caucasians and Asians. There was no risk of publication bias. In summary, the meta-analysis suggests that there is no association between FAS A670G polymorphism and susceptibility to cervical cancer in both Caucasians and Asians.

Many studies have examined the association between the GSTM1 null gene polymorphism and oral cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The PubMed and Embase databases were searched for case-control studies published up to May 2013. Data were extracted and pooled odds ratio (OR) with 95% confidence intervals (CI) were calculated. Ultimately, 39 studies, comprising of 4,704 oral cancer cases and 7,090 controls, were included. Overall, for null versus present, the pooled OR was 1.29 (95% CI = 1.20-1.40), and the heterogeneity was found in all studies. In the stratified analysis by ethnicity, significant risks were found among Asians (OR = 1.39, 95% CI = 1.27-1.53; P = 0.000 for heterogeneity), but not in Caucasians (OR = 0.99, 95% CI = 0.83-1.18; P = 0.677 for heterogeneity). In conclusion, this meta-analysis demonstrates that the GSTM1 null gene polymorphism may be an increased risk of oral cancer in Asians but not in Caucasians.

Increasing epidemiological studies have revealed the important role of methylenetetrahydrofolate reductase (MTHFR) in carcinogenesis. The association of MTHFR A1298C and MTHFR C677T polymorphisms with the risk for gastric cancer remains obscure due to inconsistent findings in independent studies among diverse ethnicities. A meta-analysis based on all available publications on this genetic association was performed. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to estimate the effect of MTHFR variants on gastric carcinogenesis. Totally, 25 eligible case-control studies were included into the meta-analysis according to the inclusion criteria. The MTHFR C677T polymorphism was demonstrated to significantly increase the susceptibility to gastric cancer (OR(T vs. C) = 1.21, 95% CI 1.10-1.34; OR(TT vs. CC )= 1.47, 95% CI 1.22-1.76; OR(TC vs. CC )= 1.20, 95% CI 1.03-1.40; OR(TT + TC vs. CC) = 1.27, 95% CI 1.10-1.47; OR(TT vs. CC + TC )= 1.29, 95% CI 1.15-1.46), whereas no significant correlation was observed when assessing the MTHFR A1298C polymorphism (OR(C vs. A )= 1.00, 95% CI 0.90-1.10; OR(CC vs. AA) = 0.99, 95% CI 0.75-1.31; OR(CA vs. AA )= 1.01, 95% CI 0.89-1.14; OR(CC + CA vs. AA) = 1.00, 95% CI 0.89-1.13; OR(CC vs. AA + CA) = 0.97, 95% CI 0.74-1.27). Subgroup analyses by ethnicity and source of controls further confirmed the findings in overall analysis. The meta-analysis suggests that the polymorphism of MTHFR C677T but not MTHFR A1298C confers a risk effect on the development of gastric cancer among Asians and Caucasians, which provides a new insight into the gastric cancer pathogenesis.

To evaluate the effect of Matrix metalloproteinase 7 -181A/G polymorphism (rs11568818) on the risk of cancer, we performed a meta-analysis.

Studies investigating the association between single-nucleotide polymorphisms (SNPs) of the methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) and cancer risk report conflicting results. To derive a more precise estimation of the relationship between MTHFD1 polymorphisms and cancer risk, the present meta-analysis was carried out.

Isocitrate dehydrogenase isoforms 1 and 2 (IDH1 and IDH2) mutations have received considerable attention since the discovery of their relation with human gliomas. The predictive value of IDH1 and IDH2 mutations in gliomas remains controversial. Here, we present the results of a meta-analysis of the associations between IDH mutations and both progression-free survival (PFS) and overall survival (OS) in gliomas. The interrelationship between the IDH mutations and MGMT promoter hypermethylation, EGFR amplification, codeletion of chromosomes 1p/19q and TP53 gene mutation were also revealed.

The association between rs13387042 polymorphism on 2q35 and breast cancer (BC) has been widely evaluated since it was first identified through genome-wide association approach. However, the results have been inconclusive. To investigate this inconsistency, we performed a meta-analysis of all available studies dealing with the relationship between the 2q35-rs13387042 polymorphism and BC.

Bevacizumab has consistently demonstrated improved progression-free survival (PFS) and response rate when combined with first-line chemotherapy for HER2-negative metastatic breast cancer (mBC). However, the lack of a significant overall survival (OS) difference continues to attract debate, and identification of patients deriving greatest benefit from bevacizumab remains elusive.

Splicing assays are commonly undertaken in the clinical setting to assess the clinical relevance of sequence variants in disease predisposition genes. A 5-tier classification system incorporating both bioinformatic and splicing assay information was previously proposed as a method to provide consistent clinical classification of such variants. Members of the ENIGMA Consortium Splicing Working Group undertook a study to assess the applicability of the scheme to published assay results, and the consistency of classifications across multiple reviewers. Splicing assay data were identified for 235 BRCA1 and 176 BRCA2 unique variants, from 77 publications. At least six independent reviewers from research and/or clinical settings comprehensively examined splicing assay methods and data reported for 22 variant assays of 21 variants in four publications, and classified the variants using the 5-tier classification scheme. Inconsistencies in variant classification occurred between reviewers for 17 of the variant assays. These could be attributed to a combination of ambiguity in presentation of the classification criteria, differences in interpretation of the data provided, nonstandardized reporting of results, and the lack of quantitative data for the aberrant transcripts. We propose suggestions for minimum reporting guidelines for splicing assays, and improvements to the 5-tier splicing classification system to allow future evaluation of its performance as a clinical tool.

Matrix Metalloproteinases (MMPs) play an important role in gastric cancer (GC). Accumulated evidence suggests that functional MMP-1 and MMP-7 gene polymorphisms are associated with several tumors. The aim of this study was to investigate two single nucleotide polymorphisms, MMP-1 -1607 1G/2G and MMP-7 -181 A/G, and their potential relationship with GC. We examined 246 GC patients and 252 age-and sex-matched controls from Sichuan province in China. Genotypes were determined using a polymerase chain reaction-restriction fragment length polymorphism strategy and DNA sequencing. We also performed a meta-analysis of relevant studies, involving 1084 cases and 1721 controls, to place our findings in a broader context. No significant relationship was observed between the MMP-1 -1607 1G/2G alleles and genotypes and the risk of GC. There were significant differences in the genotypes and allele distributions of the -181 A/G polymorphism of the MMP-7 gene between cases and controls. The -181 A allele carriers had a significantly increased risk of GC compared with -181 G allele carriers (OR=3.051, 95% CI, 1.475-6.310, P=0.002), and the AA genotype of -181 A/G was associated with an increased risk of GC compared with the AG genotype (OR=3.189, 95% CI, 1.523-6.676, P=0.001). A meta-analysis of six studies also showed a significant risk of GC associated with MMP-7 polymorphism.

quinone oxidoreductase 1 (NQO1) is a cytosolic enzyme, and the NQO1 C609T polymorphism is associated with the enzymatic activity of NQO1. Many studies were performed to assess the association between NQO1 C609T polymorphism and colorectal cancer risk, but no consensus was available up to now. We conducted a meta-analysis to examine the association between NQO1 C609T polymorphism and colorectal cancer risk, and the pooled odds ratios (OR) with their 95% confidence intervals (95% CI) were used to assess the association. Finally, 12 studies involving 4,026 cases and 4,855 controls were included into the meta-analysis. Overall, there was an obvious association between NQO1 C609T polymorphism and colorectal cancer risk (T versus C: OR = 1.28, 95% CI 1.08-1.51, P = 0.005; TT versus CC: OR = 1.60, 95% CI 1.10-2.33, P = 0.015; TT/CT versus CC: OR = 1.36, 95% CI 1.09-1.69, P = 0.006; TT versus CT/CC: OR = 1.37, 95% CI 1.05-1.80, P = 0.022). Subgroup analysis by ethnicity showed that the association was obvious in both Caucasians and Asians. Therefore, the meta-analysis provides strong evidence for the association between NQO1 C609T polymorphism and colorectal cancer risk, and the T allele of NQO1 C609T polymorphism is an important risk factor of colorectal cancer.

Published studies on the association between cyclin D1 (CCND1) G870A polymorphism and bladder cancer risk have yielded conflicting results. Thus, a systemic review and meta-analysis of published studies were performed to assess the possible association. All eligible studies of G870A polymorphism and bladder cancer risk were collected from the PubMed and the Cochrane Library. Statistical analyses were performed by Review Manager 5.0 and Stata 11.0. Significant association between G870A polymorphism and bladder cancer susceptibility was found under recessive model in overall population (OR = 1.21, 95% CI 1.01-1.45, P = 0.04). When stratifying for the race, our analysis suggested that CCND1 G870A was associated with bladder cancer risk in Asians when using homogeneous codominant (OR = 1.72, 95% CI 1.34-2.20, P < 0.0001), recessive (OR = 1.46, 95% CI 1.21-1.77, P < 0.0001), dominant (OR = 1.36, 95% CI 1.10-1.69, P = 0.004), and allelic models (OR = 1.30, 95% CI 1.15-1.47, P < 0.0001) to analyze the data. However, no significant associations were found in Caucasians. After stratifying the studies by control source, G870A polymorphism was significantly associated with bladder cancer risk under recessive model (OR = 1.31, 95% CI 1.03-1.67, P = 0.03) in hospital-based case-control studies, but not in population-based case-control studies. This meta-analysis suggested that G870A polymorphism most likely contributes to increased susceptibility to bladder cancer in the overall population, hospital-based case-control studies, and Asians.

Numerous studies have investigated the association between xeroderma pigmentosum complementation group C (XPC) poly (AT) deletion/insertion (PAT -/+) polymorphism and cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis based on 32 publications including 10,214 cases and 11,302 controls to acquire a more robust estimation of the relationship. We searched publications from MEDLINE, EMBASE and CBM which assessed the associations between XPC PAT -/+ polymorphism and cancer risk. We calculated pooled odds ratio (OR) and 95% confidence interval (CI) by using either fixed-effects or random-effects model. We found that individuals carrying the PAT +/+ genotype have significantly increased cancer risk (PAT +/+ vs.

A T-to-C polymorphism that creates a recognition site for the MspA1 restriction enzyme in the 5' promoter region of CYP17 has been implicated as a risk factor for prostate cancer. To date, many studies have evaluated associations between the CYP17 MspA1 polymorphism and prostate cancer risk; however, the results were controversial. Therefore, the aim of this study was to perform a meta-analysis to investigate the association between the CYP17 MspA1 polymorphism and the risk of prostate cancer.

The onset and development of breast cancer (BC) are influenced by many factors, including the single nucleotide polymorphism (SNP) rs2046210 at 6q25.1. However, studies of the potential association between rs2046210 at 6q25.1 and risk of BC have given inconsistent results. We performed a meta-analysis to address this controversy. PubMed, EMBASE, and Web of Science were systematically searched to identify relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the association between this SNP and risk of BC. A total of 14 studies are included in the meta-analysis, involving 123,085 cases and 120,761 controls. The A-allele, AA/GA, and AA genotypes were significantly associated with increased risk of BC (A-allele vs. G-allele: OR = 1.20, 95%CI = 1.15-1.25, P for heterogeneity < 0.0001; AA/GA vs. GG: OR = 1.22, 95%CI = 1.16-1.28, P for heterogeneity < 0.0001; AA vs.

Genetic polymorphisms in glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) genes have been widely reported and considered to have a significant effect on prostate cancer (PCa) risk, but the results are inconsistent. To evaluate the impact of the GSTM1 and GSTT1 polymorphism on PCa risk, we conducted a comprehensive meta-analysis based on 18 eligible studies. A total of 18 studies, including 7,119 subjects for GSTM1 and 6,454 subjects for GSTT1 between 1999 and 2012 were identified through researching MEDLINE, PubMed, Web of Science, EMBASE, Chinese National Knowledge Infrastructure database, and Chinese Biomedical Literature database. A meta-analysis was performed to obtain summary-estimated odd ratios and 95% confidence intervals of GSTM1 and GSTT1 polymorphisms for PCa, with attention to study quality and publication bias. Overall, there is a significant association between GSTM1 (odds ratio (OR) = 1.407, 95% confidence intervals (95% CI) = 1.147-1.727, I(2) = 73.2%, P = 0.001) genotypes and PCa susceptibility. Significant associations were also observed in subgroups of Caucasian populations (OR = 1.262, 95% CI = 1.055-1.511, I(2) = 48.7%, P = 0.011) and Asian populations (OR = 1.776, 95% CI = 1.134-2.781, I(2) = 83.4%, P = 0.012). However, no significant association was found (OR = 1.776, 95% CI = 1.134-2.781, P = 0.243) in African-American populations when stratified by ethnicity. While, there was no significant association seen between GSTT1 (OR = 1.003, 95% CI = 0.823-1.298, I(2) = 68.8%, P = 0.778) genotypes and PCa risk. However, no significant associations were observed in subgroups of Caucasian populations (OR = 1.086, 95% CI = 0.801-1.471, I(2) = 72.1%, P = 0.597) and Asian populations (OR = 0.961, 95% CI = 0.644-1.434, I(2) = 73.0%, P = 0.846), and similar result was found among African-American populations (OR = 0.802, 95% CI = 0.194-3.321, P = 0.761) when stratified by ethnicity. Our results suggest that the GSTM1 gene polymorphism contributes to PCa susceptibility, while GSTT1 gene polymorphism is not associated with PCa in our study.

RASSF1A has been reported to be a candidate tumor suppressor in non-small cell lung cancer (NSCLC). However, the association between RASSF1A promoter methylation and NSCLC remains unclear, particularly in regarding links to clinicopathologic features.