In metastatic colorectal cancer, mutation testing for KRAS exon 2 is widely implemented to select patients with wild-type tumors for treatment with the monocloncal anti-EGFR antibodies cetuximab and panitumumab. The added predictive value of additional biomarkers in the RAS-RAF-MAPK and PI3K-AKT-mTOR pathways in colorectal cancer is uncertain, which led us to systematically review the impact of alterations in KRAS (outside of exon 2), NRAS, BRAF, PIK3CA and PTEN in relation to the clinical benefit from anti-EGFR treatment.

Human p21 gene is characterized by a polymorphism at codon 31 leading to a Serine-to- Arginine (S/R), two different alleles of p21 Ser31Arg (rs 1801270) polymorphism have been shown to differ significantly in their transcriptional efficiency. More and more investigations are now being carried out to examine a possible link between the p21 Ser31Arg polymorphism and cancer. However, the results were inconclusive. Therefore, we carried out a systematic review and meta-analysis to examine whether this polymorphism is associated with gastrointestinal tract tumor in Asian. Seven studies (n = 2690), comprising 967 cases and 1723 controls in Asian population, were included in our study. The meta-analysis showed significant association between Ser-allele or Ser/Ser genotype and the susceptibility to gastrointestinal tract tumor in overall studies (Ser-allele vs. Arg-allele: OR = 1.17, 95% CI: 1.04-1.31; Ser/Ser vs. Arg/Arg: OR = 1.38, 95% CI: 1.09-1.75; Ser/Ser vs. Arg/Ser: OR = 1.27, 95% CI: 1.05-1.53; Ser/Ser vs. Arg/Ser + Arg/Arg: OR = 1.29, 95% CI: 1.07-1.54). Despite the limitations, the results of the present meta-analysis suggested that, in the p21 Ser31Arg polymorphism, Ser-allele and Ser/Ser genotype might be risk factors for gastrointestinal tract tumor in Asian populations.

It is still controversial whether X-ray repair cross-complementing group (XRCC1) gene polymorphisms (Arg194Trp and Arg399Gln) are associated with the clinical outcome of platinum-based chemotherapy in gastric cancer patients based on published studies. Meta-analysis was performed to provide a systematic review of the findings. Eligible articles from the PubMed, SinoMed, and CNKI databases before September 1, 2012, were selected. Objective response (complete response + partial response vs progressive disease + stable disease), progress-free survival (PFS) and overall survival (OS) were applied to evaluate clinical outcomes. We calculated the odds ratio or hazard risk (HR) with 95% confidence interval (CI) using the STATA software. Eleven eligible articles including 1274 gastric cancer patients with platinum-based treatment were enrolled in our meta-analysis. The results indicated that the A allele of the XRCC1 Arg399Gln polymorphism was significantly associated with poor OS (HR = 1.40; 95%CI = 1.04-1.90) of gastric cancer but not for platinum-based chemotherapy response or PFS. No significant associations were observed between XRCC1 Arg194Trp and objective response. The data suggest that the XRCC1 Arg399Gln polymorphism may be a prognostic biomarker of OS for platinum-based gastric cancer treatment. However, further cohorts with larger sample sizes from different ethnic backgrounds and with improved experimental design are needed to confirm these findings.

Mutations in the fibroblast growth factor receptor-3 (FGFR3) gene are frequently found in bladder cancer, but their prognostic value remains controversial. To globally summarize the association between FGFR3 mutations and the grade and stage of bladder cancer, and to analyze the predictive role of FGFR3 mutations with respect to survival, eligible studies were identified and assessed for quality through multiple search strategies. Risk ratio (RR) data were collected from studies comparing the number of FGFR3 mutants among low-grade and early-stage bladder cancer patients to the number among high-grade and late-stage patients. Hazard ratio (HR) data were collected from studies comparing survival in patients with mutant FGFR3 genes to those with wild-type genes. Studies were pooled, and the RRs of grade and stage and the HRs of survival were calculated. Thirty studies were included in the present meta-analysis. FGFR3 mutations were found to be closely associated with low-grade and early-stage bladder cancer, showing pooled RRs = 2.948 [95% confidence interval (CI) = 2.357-3.688] and 2.845 (95%CI = 2.145- 3.773), respectively. Notably, patients with FGFR3 mutations tended to show better disease-, progress-, and recurrence-free survival (HR = 0.561, 95%CI = 0.405-0.779), and better disease-specific survival (HR = 0.363, 95%CI = 0.266-0.496). This study demonstrated that FGFR3 mutations are closely related to low grade, early stage, and better survival among bladder cancer patients.

The TP53BP1 gene may be involved in the development of cancer through disrupting DNA repair. However, studies investigating the relationship between TP53BP1 Glu353Asp (rs560191) polymorphism and cancer yielded contradictory and inconclusive outcomes. In order to realize these ambiguous findings, a meta-analysis was performed to assess the association between the TP53BP1 Glu353Asp (rs560191) polymorphism and susceptibility to cancer.

Fas and its ligand (FasL) play an important role in apoptosis and carcinogenesis. Therefore, the potential association of polymorphisms in the Fas (-670A>G, rs1800682; -1377G>A, rs2234767) and FasL (-844C>T, rs763110) with cancer risk has been widely investigated. However, all the currently available results are not always consistent. In this work, we performed a meta-analysis to further determine whether carriers of the polymorphisms in Fas and FasL of interest could confer an altered susceptibility to cancer. All relevant data were retrieved by PubMed and Web of Science, and 52 eligible studies were chosen for this meta-analysis. There was no association of the Fas -670A>G polymorphism with cancer risk in the pooled data. For the Fas -1377G>A and FasL -844C>T polymorphisms, results revealed that the homozygotes of -1377A and -844C were associated with elevated risk of cancer as a whole. Further stratified analysis indicated markedly increased risk for developing breast cancer, gastric cancer, and esophageal cancer, in particular in Asian population. We conclude that carriers of the Fas-1377A and the FasL -844C are more susceptible to the majority of cancers than non-carriers.

Colorectal cancer (CRC) is a heterogeneous disease with multiple underlying causative genetic mutations. The B-type Raf proto-oncogene (BRAF) plays an important role in the mitogen-activated protein kinase (MAPK) signaling cascade during CRC. The presence of BRAFV600E mutation can determine the response of a tumor to chemotherapy. However, the association between the BRAFV600E mutation and the clinicopathological features of CRC remains controversial. We performed a systematic review and meta-analysis to estimate the effect of BRAFV600E mutation on the clinicopathological characteristics of CRC.

Many studies have shown that microRNAs (miRNAs) could play a potential role as prognostic biomarkers of tumors. The aim of this study is to summarize the global predicting role of microRNA-210 (miR-210) for survival in patients with a variety of carcinomas.

While the vast majority of patients with thyroid cancer have an excellent prognosis, those with more aggressive courses experience significant morbidity and mortality. Advanced forms of thyroid cancer are typically refractory to standard therapy. Numerous agents with potential usefulness in the treatment of advanced thyroid cancer have recently come under study.

To investigate our clinical experience with the colonic manifestations of phosphatase and tensin homolog on chromosome ten (PTEN) hamartoma tumor syndrome (PHTS) and to perform a systematic literature review regarding the same.

Sphingosine kinase 1 (SK1) is a key regulator of the dynamic ceramide/sphingosine 1-phosphate rheostat balance and important in the pathological cancer genesis, progression, and metastasis processes. Many studies have demonstrated SK1 overexpressed in various cancers, but no meta-analysis has evaluated the relationship between SK1 and various cancers.

MiRNAs are important regulators of different biological processes, including tumorigenesis. MiR-210 is a potential prognostic factor for survival in patients with cancer according to previous clinical researches. We conducted a systematic review and meta-analysis to summarize the significance of increased miR-210 expression in the prognosis of indicated cancers.

Abnormal regulation of apoptosis can lead to carcinogenesis. Single nucleotide polymorphisms in apoptotic genes have been associated with cancer risk, such as the FAS rs2234767G/A polymorphism, which alters transcription of the FAS promoter. Downregulation of FAS, with resultant cellular resistance to death signals, has been found in many cancers. However, the association between the FAS rs2234767G/A polymorphism and cancer risk is still controversial. Here, we performed a meta-analysis including 41 articles (44 case-control studies, 17,814 cases and 24,307 controls) identified from PubMed and Chinese language (CNKI and WanFang) databases related to cancer susceptibility and the FAS rs2234767G/A polymorphism. We used odds ratios (ORs) and 95% confidence intervals (CIs) to assess the strength of the associations. We found that the rs2234767 G-allele was a protective factor for cancer risk (GG vs. AA: OR=0.88, 95% CI=0.79-0.98; GG+GA vs. AA: OR=0.87, 95% CI=0.79-0.96). Similar associations were detected in the "source of control", ethnicity, and cancer type subgroups. Further studies on a larger sample size and considering gene-environment interactions should be conducted to confirm the role of FAS polymorphisms, especially rs2234767G/A, in cancer risk.

This meta-analysis investigates the oncological safety of breast-conserving therapy BCT in BRCA-mutation carriers and the risk for contralateral breast cancer (CBC) compared with non-carriers, potential risk factors for ipsilateral breast recurrence (IBR) or CBC and grades these factors based on the level of evidence. A PubMed search was conducted through April 2013 to identify studies that described the risk for IBR and CBC after BCT in BRCA-mutation carriers versus non-carriers as well as studies that investigated risk factors for IBR and CBC in BRCA-mutation carriers. Results were summarized using meta-analysis when sufficient studies were available. Ten studies investigated the oncological safety of BCT in BRCA-mutation carriers versus non-carriers. There was no significant difference in IBR between carriers and controls (RR 1.45, 95 % CI 0.98-2.14). However, a significant higher risk for IBR in BRCA-mutation carriers was observed in studies with a median follow-up ≥7 years (RR 1.51, 95 % CI 1.15-1.98). CBCs were significantly greater in carriers versus controls (RR 3.56, 95 % CI 2.50-5.08). Use of adjuvant chemotherapy and oophorectomy were associated with a significantly lower risk for IBR in BRCA-mutation carriers. Three factors were associated with a lower risk for CBC in BRCA-mutation carriers: oophorectomy, use of tamoxifen, and age at first breast cancer. Based on current evidence, the use of BCT in BRCA-mutation carriers can be considered a reasonable option since it does not seem to increase the risk for IBR. However, several aspects should be taken into account before the final decision-making.

Previous studies demonstrated that MicroRNA-92a (miR-92a) was significantly differential expressed between colorectal cancer (CRC) patients and control cohorts, which provide timely relevant evidence for miR-92a as a novel promising biomarker in the colorectal cancer patients. This meta-analysis aimed to evaluate potential diagnostic value of plasma miR-92a.

More than 200 articles have been published in the past 20 years on associations between genetic variants and risk of cervical cancer but the results have generally been inconsistent.

To explore the association of the androgenic receptor (AR) CAG repeats with the risks of benign prostatic hyperplasia (BPH) and prostate cancer (PCa).

A significant proportion of squamous cell carcinomas of the oropharynx (OP-SCC) are related to human papillomavirus (HPV) infection and p16 overexpression. This subgroup proves better prognosis and survival but no evidence exists on the correlation between HPV and p16 overexpression based on diagnostic measures and definition of p16 overexpression. We evaluated means of p16 and HPV diagnostics, and quantified overexpression of p16 in HPV-positive and -negative OP-SCCs by mode of immunohistochemical staining of carcinoma cells.

Ovarian cancer is the leading cause of cancer-related death in women. This meta-analysis was conducted to evaluate the association of transforming growth factor β receptor I (TβR-I) 6A/9A gene polymorphism with ovarian cancer risk. The association literatures were identified from PubMed and Cochrane Library on 1 October 2013, and eligible reports were recruited and synthesized. Four reports were recruited into this meta-analysis for the association of TβR-I 6A/9A gene polymorphism with ovarian cancer risk. 6A allele and 6A/6A genotype of TβR-I were associated with the ovarian cancer risk (6A: OR = 1.24, 95% CI: 1.02-1.51, p = 0.03; 6A/6A: OR = 2.30, 95% CI: 1.01-5.22, p = 0.05). However, TβR-I 9A/9A genotype was not associated with the risk of ovarian cancer (OR = 0.82, 95% CI: 0.66-1.02, p = 0.08). In conclusion, TβR-I 6A allele and 6A/6A genotype are associated with the ovarian cancer risk. However, more studies should be performed to confirm this relationship in the future.

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.