Association studies of germline DNA repair single nucleotide polymorphisms (SNPs) and glioma risk have yielded inconclusive results. We therefore performed a systematic review and meta-analysis of studies investigating this association.

In the present study, we performed this meta-analysis to estimate the association between excision repair cross-complementation group 1 (ERCC1) gene polymorphism and clinical resistance to platinum-based chemotherapy in the patients with epithelial ovarian cancer (EOC).

T3801C is a common polymorphism in CYP1A1, showing differences in its biological functions. Case-control studies have been performed to elucidate the role of T3801C in cancer, although the results are conflicting and heterogeneous. Hence, we performed a meta-analysis to investigate the association between cancer susceptibility and T3801C (55,963 cases and 76,631 controls from 268 studies) polymorphism in different inheritance models.We used odds ratios with 95% confidence intervals to assess the strength of the association. Overall, significantly increased cancer risk was observed in any genetic model (dominant model: odds ratio [OR]=1.14, 95% confidence interval [CI]=1.09–1.19; recessive model: OR=1.23, 95% CI=1.12–1.34; CC vs. TT: OR=1.31, 95% CI=1.19–1.45; TC vs. TT: OR=1.12, 95% CI=1.07–1.18; additive model: OR=1.14, 95% CI=1.09–1.19) when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, the elevated risk remained for subgroups of cervical cancer, head and neck cancer, hepatocellular cancer, leukemia, lung cancer, prostate cancer and breast cancer. In addition, significantly decreased colorectal cancer risk was also observed. In summary, this meta-analysis suggests that the participation of CYP1A1 T3801C is a genetic susceptibility for some cancer types.Moreover, our work also points out the importance of new studies for T3801C association in some cancer types, such as gallbladder cancer, Asians of acute myeloid leukemia, and thyroid cancer, where at least some of the covariates responsible for heterogeneity could be controlled, to obtain a more conclusive understanding about the function of the CYP1A1 T3801C polymorphism in cancer development.

Manganese superoxide dismutase (MnSOD) inhibits oxidative damage and cancer therapy effectiveness. A polymorphism in its encoding gene (SOD2: Val16Ala rs4880) may confer poorer breast cancer survival, but data are inconsistent. We examined the association of SOD2 genotype and breast cancer recurrence (BCR) among patients treated with cyclophosphamide-based chemotherapy (Cyclo). We compared our findings with published studies using meta-analyses.

Insulin receptor substrate-2 (IRS-2), a signaling adaptor protein, was involved in two cancer-related pathways (the phosphatidylinositol 3'-kinase (PI3K) and the extracellular signal-regulated kinase (ERK) pathways). Several studies have evaluated the association between IRS2 rs1805097 (G>A) polymorphisms and the risk of colorectal and breast cancer. However, the results were inconsistent.

Previous studies on the association of X-ray repair cross-complementing group 1 (XRCC1) Arg194Trp, Arg399Gln, and Arg280His polymorphisms with head and neck cancer (HNC) have produced inconsistent results. The aim of the present study was to evaluate the effects of these three polymorphic variants on HNC risk.

We propose to make use of the wealth of underused DNA chip data available in public repositories to study the molecular mechanisms behind the adaptation of cancer cells to hypoxic conditions leading to the metastatic phenotype. We have developed new bioinformatics tools and adapted others to identify with maximum sensitivity those genes which are expressed differentially across several experiments. The comparison of two analytical approaches, based on either Over Representation Analysis or Functional Class Scoring, by a meta-analysis-based approach, led to the retrieval of known information about the biological situation - thus validating the model - but also more importantly to the discovery of the previously unknown implication of the spliceosome, the cellular machinery responsible for mRNA splicing, in the development of metastasis.

Epidermal growth factor receptor (EGFR) is a member of the tyrosine kinase receptor family, which is thought to be involved in the development of cancer, as the EGFR gene is often amplified, and/or mutated in cancer cells. Lung cancer remains one of the most major causes of morbidity and mortality worldwide, accounting for more deaths than any other cancer cause. Gene polymorphism factor has been reported to be an important factor which increases the susceptibility of lung cancer. There lacks a well-documented diagnostic approach for the lung cancer risk, and the etiology of lung cancer is not clear. The current systematic review was performed to explore the association of EGFR gene polymorphism with lung cancer risk. In this review, association of EGFR 181946C > T, 8227G > A gene polymorphism with lung cancer was found, and EGFR Short genotype of cytosine adenine repeat number polymorphism was significantly associated with an increased risk of lung cancer.

Cytotoxic T-lymphocyte antigen-4 (CTLA4, CD152) is one of the most fundamental immunosuppressive cytokines that inhibits T-cell activation and terminates the T-cell response by blocking signals stimulated via CD28. A number of studies have assessed the association between CTLA-4 +6230G/A polymorphism and cancer risk. However, the results remain controversial.

Bone metastasis accounts for the vast majority of breast cancer (BC) metastases, and is related to a high rate of morbidity and mortality. A number of seminal studies have uncovered gene expression signatures involved in BC development and bone metastasis; each of them points at a distinct step of the 'invasion-metastasis cascade'. In this review, we provide most recently discovered functions of sets of genes that are selected from widely accepted gene signatures that are implicate in BC progression and bone metastasis. We propose a possible sequential pattern of gene expression that may lead a benign primary breast tumor to get aggressiveness and progress toward bone metastasis. A panel of genes which primarily deal with features like DNA replication, survival, proliferation, then, angiogenesis, migration, and invasion has been identified. TGF-β, FGF, NFκB, WNT, PI3K, and JAK-STAT signaling pathways, as the key pathways involved in breast cancer development and metastasis, are evidently regulated by several genes in all three signatures. Epithelial to mesenchymal transition that is also an important mechanism in cancer stem cell generation and metastasis is evidently regulated by these genes. This review provides a comprehensive insight regarding breast cancer bone metastasis that may lead to a better understanding of the disease and take step toward better treatments.

To date, no scientific consensus about the associations of DR4 C626G, A683C, A1322G, and G422A polymorphisms with cancer risk has been reached. Therefore, we conducted a meta-analysis to assess the associations. This meta-analysis involved 16 studies, of which 15 (4,261 cases and 4,598 controls) described C626G genotypes, 8 (2,898 cases and 3,135 controls) described A683C genotypes, 6 (1,564 cases and 1,673 controls) described A1322G genotypes, and 5 (584 cases and 607 controls) described A683C genotypes. We associated all the four polymorphisms with cancer risk. The C626G polymorphism was associated with slightly elevated cancer risk in recession model comparison [odds ratio (OR)=1.12, 95 % confidence interval (CI)=1.00-1.26, P heterogeneity=0.425]. In the subgroup analysis by cancer type, significantly elevated cancer risks were found among groups with lung cancer for heterozygote comparison (OR=1.76, 95 % CI=1.00-3.09, P heterogeneity=0.863). The A1322G polymorphism was associated with significantly elevated cancer risk in the different models (heterozygote comparison: OR=1.21, 95 % CI=1.00-1.46, P heterogeneity=0.347; dominant model: OR=1.21, 95 % CI=1.01-1.46, P heterogeneity=0.189; allele model comparison for G allele vs. A allele: OR=1.17, 95 % CI=1.02-1.35, P heterogeneity=0.173). The A683C and G422A polymorphisms were not associated with cancer risk in all genetic models. The C626G and A1322G polymorphisms are associated with increased cancer risk, but the A683C polymorphism is rarely associated with cancer risk.

Evidence suggested that the -174G>C and -634C>G polymorphisms in interleukin-6 (IL6) promoter region may modulate risk of lung cancer; however, the conclusion was still inconclusive. Therefore, we performed this meta-analysis to determine the association between IL6 -174G>C and -634C>G polymorphisms and lung cancer risk. The association strength was measured by odds ratios (ORs) and 95% confidence intervals (CI). Egger's test and Begg's test were performed to detect potential publication bias. By searching PubMed, EMBASE and China National Knowledge Infrastructure, we included 16 eligible studies in this meta-analysis, involving 6,202 lung cancer cases and 7,067 controls. Five studies about -174G>C polymorphism and 11 studies about -634C>G polymorphism were analyzed. By pooling eligible studies, we found no significant association of -174G>C with lung cancer risk (C vs. G: OR = 1.029; 95% CI, 0.957-1.106; heterogeneity, P = 0.478) and no statistic association of -634C > G with lung cancer susceptibility (G vs. C: OR = 1.050; 95% CI, 0.893-1.235; Heterogeneity, P < 0.001). No significant publication bias was observed. In conclusion, we found that -634C>G and -174G>C polymorphisms in IL6 promoter region were not associated with lung cancer risk.

X-ray repair cross-complementing group 1 (XRCC1) plays an important role in the maintenance of the genomic integrity. Previous studies on the association between XRCC1 Arg194Trp polymorphism and prostate cancer risk reported conflicting results. To get a more precise assessment of the association between XRCC1 Arg194Trp polymorphism and prostate cancer risk, we performed a meta-analysis of previously published studies. Eligible studies were searched in PubMed, Embase, and China National Knowledge Infrastructure (CNKI) databases. Nine studies with a total of 5,407 subjects were finally included into the meta-analysis. Odds ratio (OR) with 95% confidence interval (95%CI) was used to assess the association. Overall, there was no obvious association between XRCC1 Arg194Trp polymorphism and prostate cancer risk (Trp vs. Arg: OR = 1.02, 95%CI 0.84-1.25, P = 0.824; TrpTrp vs. ArgArg: OR = 1.17, 95%CI 0.83-1.66, P = 0.374; TrpTrp/ArgTrp vs. ArgArg: OR = 1.00, 95%CI 0.79-1.28, P = 0.990; TrpTrp vs. ArgArg/ArgTrp: OR = 1.20, 95%CI 0.85-1.68, P = 0.301). Subgroup analysis according to ethnicity also detected no significant association in both Asians and Caucasians. In conclusion, the meta-analysis suggests that there is no obvious association between XRCC1 Arg194Trp polymorphism and prostate cancer risk.

Increasing scientific evidences suggest that CDH1 gene promoter polymorphism and DNA methylation may contribute to the development and progression of bladder cancer, but many existing studies have yielded inconclusive results. This meta-analysis aims to assess the role of CDH1 gene promoter polymorphism and methylation in bladder carcinogenesis. An extensive literature search for relevant studies was conducted in PubMed, Embase, Web of Science, Cochrane Library, and CBM databases from their inception through April 1, 2013. This meta-analysis was performed using the STATA 12.0 software. The crude odds ratio with 95% confidence interval was calculated. Fifteen studies were included in this meta-analysis with a total of 824 bladder cancer patients and 818 healthy controls being assessed. Our meta-analysis revealed that the A variant of CDH1 -160C/A polymorphism was associated with an increased risk of bladder cancer. Further analysis by pathological subtype indicated that patients with invasive carcinoma had a higher frequency of CDH1 -160A variant than those with superficial carcinoma. We analyzed the methylation frequency of CDH1 gene in 608 bladder cancer samples and 338 normal bladder samples. Our data strongly suggest that the CDH1 promoter methylation frequencies in bladder cancer tissues were greater than those in normal control tissues. In conclusion, our meta-analysis indicates that promoter polymorphism and methylation of CDH1 gene may be involved in the development and progression of bladder cancer. CDH1 gene promoter polymorphism and methylation might be promising biomarkers for the diagnosis and prognosis of bladder cancer.

Evidence has shown that matrix metalloproteinases-3 (MMP3) is important for cancer progression. Recent studies about the association between the -1171(5A>6A) polymorphism in MMP3 promoter region and cancer risk have yielded conflicting results.

Forkhead box E1 encodes the transcription factor FOXE1 (or TTF-2), which together with Homeobox protein NKX2-1, PAX8 and HHEX, are pivotal proteins required for thyroid gland formation, differentiation and function. Recently, genome-wide association studies have identified FOXE1 as a thyroid cancer (TC) susceptibility gene in populations of European descent. After that, a number of studies reported that the rs965513, rs1867277, and rs71369530 polymorphism in FOXE1 has been implicated in TC risk. However, the causal variants remain unknown. To derive a more precise estimation of the relationship, a meta-analysis of 9,828 TC cases and 109,995 controls from 14 case-control studies was performed. Overall, significant results were observed for rs965513 (OR=1.71, 95% CI: 1.59-1.85, P<10(-5)), rs1867277 (OR=1.64, 95% CI: 1.51-1.78, P<10(-5)) and rs71369530 (OR=2.01, 95% CI: 1.66-2.44, P<10(-5)) polymorphism. In the subgroup analysis by ethnicity, we found that rs965513 polymorphism confer high risk for Caucasians with per-allele OR of 1.80 (95% CI: 1.69-1.92, P<10(-5)) compared to East Asians of 1.35 (95% CI: 1.09-1.67, P=0.006). There was strong evidence of heterogeneity, which largely disappeared after stratification by ethnicity. In the subgroup analysis by sample size, and study design, significantly increased risks were found for the polymorphism. In conclusion, this meta-analysis demonstrated that common variations of FOXE1 are a risk factor associated with increased TC susceptibility.

Poly (ADP-ribose) polymerase-1 (PARP-1) plays critical roles in the detection and repair of damaged DNA, as well as cell proliferation and death. Numerous studies have examined the associations between PARP1 Val762Ala (rs1136410 T>C) polymorphism and cancer susceptibility; nevertheless, the findings from different research groups remain controversial.

In the X-ray repair cross-complementing group 1 (XRCC1) gene, a polymorphism, Arg399Gln (rs25487), has been shown to change neoconservative amino acid and thus result in alternation of DNA repair capacity. Numerous studies have investigated the association between Arg399Gln and breast cancer risk in the American population, but yielding inconsistent results. This study aimed to clarify the role of this polymorphism in susceptibility to breast cancer.

Many studies have been conducted to explore the association between p53 codon 72 polymorphism and prostate cancer (PCa). However, the results remain inconsistent. Therefore, we performed a large meta-analysis of relevant studies to determine a more precise estimation of this relationship. Systematic searches of the electronic databases PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure (CNKI) up to October 2013 were performed. Fixed or random-effects meta-analytical models were used to calculate the summary odds ratio (OR) and corresponding 95% confidence intervals (CIs). Meta-regression, Galbraith plots, subgroup analysis, and sensitivity analysis were also performed. The study included 17 case-control studies involving 2,371 PCa cases and 2,854 controls. Our results showed that the p53 codon 72 polymorphism was not associated with PCa risk in all genetic models in the overall populations. When limiting the meta-analysis to the studies conforming to Hardy-Weinberg equilibrium, the pooled analyses showed a significant association between p53 codon 72 polymorphism and PCa in a Caucasian population in co-dominant model Pro/Pro vs. Arg/Arg (OR = 1.57, 95% CI = 1.08-2.28, P = 0.017) and recessive model Pro/Pro vs. (Arg/Pro + Arg/Arg) (OR = 1.60, 95% CI = 1.12-2.27, P = 0.009). In subgroup analysis stratified by PCa stages and Gleason grades, a slight but significant association was found when advanced PCa was compared with localized PCa only in recessive model Pro/Pro vs. (Arg/Pro + Arg/Arg) (OR = 1.51, 95% CI = 1.02-2.23, P = 0.039). This meta-analysis suggested that the Pro/Pro genotype of p53 codon 72 polymorphism was associated with increased prostate cancer risk, especially among Caucasians.

Methylenetetrahydrofolate reductase (MTHFR) is a central enzyme involved in regulating the metabolic function of folate, which plays a pivotal role in DNA synthesis, repair, and methylation. The role of MTHFR C677T polymorphism in oral cancer risk has been reported with conflicting evidence. We conducted this study to appropriately estimate the effect size. We searched eligible studies in medicine-specific databases (PubMed, EMBASE, and Web of Knowledge) using (polymorphism) OR (polymorphisms) AND (methylenetetrahydrofolate reductase) OR (MTHFR) AND (oral cancer). A total of seven studies were summarized. This meta-analysis of the combined data showed a marginal association of MTHFR C677T polymorphism with oral cancer risk [odds ratio (OR) = 0.86, 95% confidence interval (CI) = 0.73-1.00 for CT vs. CC]. We also found decreased oral cancer risk in Asian population and hospital-based studies. Moreover, heavy drinkers were found to have a significantly higher risk of developing such cancer as compared to the non-heavy drinkers. These results suggest that MTHFR C677T polymorphism may play a role in oral cancer carcinogenesis in Asian population and heavy drinkers.