In recent years, over 1000 reports have been published on the association between hepatic diseases and gene mutations which may result in pathogenic amino acids. Most of the studies focus on the hepatocellular carcinoma (HCC). The aim was to systematically examine the published literature on the association between the mutations of arginine, serine, and threonine and hepatic diseases, particularly HCC. The Biosciences information service database was systematically searched before July 10, 2012. Of the initially selected 471 publications, 112 articles were included in this study. Meta-analyses were conducted for 3 amino acids. Risk ratios were used to analyze the association between amino acids and liver diseases. We analyze the literature on the association between gene mutations and hepatic diseases, especially in patients with HCC. Full-text articles were analyzed by 4 independent researchers. Some amino acid mutations were found only in people with liver diseases--not in the general population. Arginine and threonine mutations occurred more frequently in patients with hepatic diseases, compared to the normal population. There is a statistically significant association between arginine mutations and the risk of HCC and serine mutations and the risk of HCC.

The survival rate of colorectal cancer (CRC) patients carrying wild-type KRAS is significantly increased by combining anti-EGFR monoclonal antibody (mAb) with standard chemotherapy. However, conflicting data exist in both the wild-type KRAS and mutant KRAS groups, which strongly challenge CRC anti-EGFR treatment. Here we conducted a meta-analysis in an effort to provide more reliable information regarding anti-EGFR treatment in CRC patients.

The interleukin (IL)-1β-511 C/T polymorphism has been shown to be functional and to contribute to the risk of gastric cancer. However, the relationship between the IL-1β-511 C/T polymorphism and gastric carcinogenesis remains inconclusive. A systematical electronic search was conducted of the MEDLINE, EMBASE, and CENTRAL databases. A random and a fixed effects model were exploited to estimate summary odds ratios and 95 % confidence intervals. Subgroup and sensitivity analyses were carried out with respect to ethnicity, quality assessment scores, control sources, genotyping methods, cancer histopathology and location, and Helicobacter pylori (H. pylori) infection. A total of 45 studies containing 9,066 cases of gastric cancer and 11,192 control subjects satisfied the inclusion criteria. The IL-1β-511 C/T polymorphism was found to enhance the risk of stomach cancer for overall and HWE-satisfying studies. Asians showed a positive relationship in both the overall and HWE-satisfying groups, whereas Caucasians did not. Based on subgroup analysis, H. pylori infection and genotype analysis using PCR-RFLP methods increase the association between IL-1β-511 T allele carrier and risk of stomach cancer. A positive relationship was found between the IL-1β-511 C/T SNP and stomach carcinoma susceptibility, and the results suggest that Asian ethnicity, H. pylori infection and methodologically, PCR-RFLP genotyping strengthen this relationship. Reflecting on prevalence of H. pylori in Asian countries, additional studies on the IL-1β-511 C/T SNP in the context of ethnicity and H. pylori infection may provide key insights into the mechanism underlying gastric cancer carcinogenesis. It was found PCR-RFLP is the most reliable genotyping method, and thus, it is recommendable to adopt it to determine the presence of the IL-1β-511 C/T SNP.

Many studies have reported detection of aberrant methylation of genes in stool sample for early colorectal cancer (CRC) or adenomas had high sensitivity and specificity, but still remained controversial. We aimed to evaluate the diagnostic value of stool testing for markers of CRC and adenomas.

African American men (AA) exhibit a disproportionate share of prostate cancer (PRCA) incidence, morbidity, and mortality. Several genetic association studies have implicated select 8q24 loci in PRCA risk in AA. The objective of this investigation is to evaluate the association between previously reported 8q24 risk alleles and PRCA in African-Barbadian (AB) men known to have high rates of PRCA.

Catalase (CAT) activity is likely to be affected by functional polymorphism of C-262 T (rs1001179) in the CAT gene (OMIM: 115500). It is hypothesized that individuals with the lower expressing forms of the CAT polymorphism may be more susceptible to breast cancer. Therefore, the present case-control study and meta-analysis were carried out. The present case-control study consisted of 407 females with breast cancer and a total of 395 healthy female from population matched with patients according to age. Genotypic analysis for the CAT C-262 T polymorphism was determined by PCR. We identified 7 eligible studies, including 10,471 subjects (4,959 patients, and 5,512 healthy controls) in relation to the CAT C-262 T polymorphism and breast cancer risk. Based on the present case-control study, the CT (OR = 0.90, 95% CI: 0.66-1.22, P = 0.484) and TT (OR = 0.68, 95% CI: 0.35-1.30, P = 0.245) genotypes were not associated with breast cancer risk compared to the CC genotype. For meta-analysis including all studies, there was significant heterogeneity between studies. The overall ORs of the breast cancer risk were not associated with the CT (Q-statistic = 14.90, df = 6, P < 0.05; OR = 1.01, 95% CI: 0.92-1.09, P = 0.862) and TT (Q-statistic = 2.57, df = 6, P > 0.05; OR = 1.03, 95% CI: 0.85-1.24, P = 0.770) genotypes. There was no association between C-262 T polymorphism of the CAT and risk of breast cancer.

Imatinib mesylate, a competitive tyrosine kinase inhibitor, is considered the first-line therapy drug for Ph+ chronic myeloid leukemia (CML). Three single-nucleotide polymorphisms (SNPs) in the ATP-binding cassette, subfamily B (MDR/TAP), member 1 gene (ABCB1/MDR1), c.1236C>T, c.2677G>T/A and c.3435C>T, have been shown to affect cellular transport/metabolism of imatinib. The associations between these SNPs and imatinib response in CML patients have been widely evaluated, but the results were inconsistent. To derive a conclusive assessment of the associations, we performed a meta-analysis by combining data from a total of 12 reports including 1826 patients. The results showed that the 2677G allele or 3435T allele predicted a worse response to imatinib in CML patients, whereas 1236CC genotype was associated with better response in CML patients from Asian region. In conclusion, this meta-analysis suggests that c.1236C>T, c.2677G>T/A and c.3435C>T can be served as predictive markers for the therapeutical use of imatinib in CML patients.

The goal of this study is to examine whether vitamin D receptor (VDR) polymorphisms are associated with the susceptibility to breast cancer. Meta-analysis was employed to investigate the association between the VDR FokI, BsmI, ApaI, and TaqI polymorphisms and the incidence of breast cancer.A total of 32 comparative studies were evaluated in this meta-analysis, which included 17,067 patients and 20,843 controls. Meta-analysis of the VDR FokI polymorphism indicated an association between the incidence of breast cancer and the ff genotype in Europeans (OR = 1.126, 95% CI = 1.026-1.243, p = 0.019). Furthermore, an association between the incidence of breast cancer and the VDR FokI polymorphism was found in the Europeans using the allele contrast, as well as the homozygote contrast. However, the meta-analysis indicated no association between breast cancer and the BsmI polymorphism in all study subjects, including the Europeans (OR for the B allele = 0.996, 95% CI = 0.964-1.097, p = 0.930, 1.026, 95% CI = 0.929-1.134, p = 0.610). Moreover, breast cancer incidence was not associated with the ApaI and Taq polymorphisms (OR for the A allele = 0.908, 95% CI = 0.763-1.041, p = 0.167, OR for the T allele = 0.972, 95% CI = 0.929-1.017, p = 0.221).This meta-analysis suggests that the VDR FokI polymorphism is associated with susceptibility to breast cancer in the European population.

Genetic mutations have been found to be associated with thyroid cancer. Previous studies have been focused on the relation between genetic mutations and thyroid cancer. We sought to evaluate the prognostic value of the three most common genetic mutations (BRAF, RAS, and RET) in patients with thyroid cancer.

Current procedures for diagnosis and biomarker examination of colorectal cancer (CRC) are invasive and unpleasant. There is a great need to identify sensitive and specific biomarkers for early diagnosis of CRC. Circulating microRNAs (miRNAs) are promising molecular markers for CRC prediction. We performed a comprehensive meta-analysis to integrate an evaluation index for diagnostic accuracy of circulating miRNAs in diagnosing CRC patients. Furthermore, we conducted an independent validation set of 49 CRC patients and 49 healthy controls. In our meta-analysis, we found that miR-21 yielded a pooled area under ROC curve (AUC) of 0.867 (sensitivity: 76%, specificity: 82%) in discriminating CRC from controls, and miR-92a yielded a summary AUC of 0.803 (sensitivity: 77%, specificity: 68%); miR-21 had a higher diagnostic efficiency than miR-92a. In the further validation, plasma miR-21 levels in CRC patients were significantly higher than levels observed in healthy subjects. A ROC curve analysis showed a consistent result. However, this phenotype was not present in miR-92a. Moreover, the expression trend of miR-21 in plasma samples was in line with that of tissue samples, along with the cellular level. Current evidences suggest that plasma miR-21 could be a reliable and non-invasive biomarker for CRC diagnosis. Studies with larger cohorts that include the diagnostic value of plasma miR-21 for CRC are warranted.

The objective of this meta-analysis was to systematically assess the survival benefit of aspirin use before or after diagnosis for patients with colorectal cancer (CRC).

The apurinic/apyrimidinic endonuclease 1 (APE1) plays important roles in the repair of DNA damage and adducts. However, previous case-control studies on the association between the APE1 Asp148Glu polymorphism and prostate cancer susceptibility have shown contradictory results, this meta-analysis was performed to draw a more precise estimation of the relationship. A total of seven case-control studies including 1,294 cases and 1,762 controls were included for analysis. In overall, no significant associations were found in all genetic models (GG vs. TT: OR = 1.16, 95 % CI 0.89-1.52; TG vs. TT: OR = 1.04, 95 % CI 0.81-1.35; the dominant model GG + TG vs. TT: OR = 1.12, 95 % CI 0.96-1.30; the recessive model GG vs. TG + TT: OR = 0.90, 95 % CI 0.77-1.04); in the subgroup by source of control, we found a significant association for the dominant model in Hospital-based subgroup (OR = 1.34, 95 % CI 1.08-1.68), no significant associations were found in other models in the subgroups. This meta-analysis suggested that the APE1 Asp148Glu polymorphism was a risk factor for prostate cancer susceptibility in Hospital-based population.

MET is a receptor present in the membrane of NSCLC cells and is known to promote cell proliferation, survival and migration. MET gene copy number is a common genetic alteration and inhibition o MET emerges as a promising targeted therapy in NSCLC. Here we aim to combine in a meta-analysis, data on the effect of high MET gene copy number on the overall survival of patients with resected NSCLC.

Previous studies evaluating the association between the XPG Asp1104His polymorphism and melanoma susceptibility remained controversial. To draw a more precise estimation of the relationship, a total of eight published case-control studies containing 5,212 cases and 7,045 controls were included for meta-analysis. Overall, a significant association was found between the XPG Asp1104His polymorphism and melanoma susceptibility for the dominant model (OR = 2.42, 95 % CI = 2.26-2.60). In subgroup analysis by source of control, there was an obvious association was found among Population-based subgroup for the dominant model CC+GC vs GG (OR 2.51, 95 % CI 2.28-2.77), among the Hospital-based subgroup, an obvious association was also found for the dominant model CC+GC vs GG (OR 2.34, 95 % CI 2.12-2.58). This meta-analysis suggested that the XPG Asp1104His polymorphism was a risk factor for melanoma susceptibility.

O(6)-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair gene. Epigenetic silencing of the MGMT promoter methylation compromises DNA repair and has been associated with longer survival in patients with glioblastoma (GBM) who receive alkylating agents. But the prognostic of MGMT promoter methylation in GBM patients of different race is still ambiguous. Based on an univariate or multivariate analysis between different race (Caucasian and Asian), a meta-analysis of the effects of MGMT promoter methylation on both progression-free survival (PFS) and overall survival (OS) among GBM patients was conducted. A total of 6,309 patients from 50 studies were involved in the analysis. Random effect models were applied to estimate the pooled hazard ratio (HR) with 95 % confidence intervals (CIs) for GBM patients of different race prognosis, the Chi square-based Q test was used to test heterogeneity. Begg's (funnel plot method) and Egger's linear regression tests were adopted to check publication bias (a bias with regard to what is likely to be published, among what is available to be published). The HR value estimated for OS was 0.524 (95 % CI 0.428-0.640) by univariate analysis and 0.427 (95 % CI 0.355-0.513) by multivariate analysis in Caucasian. The HR value estimated for OS was 0.892 (95 % CI 0.469-1.698) by univariate analysis and 0.562 (95 % CI 0.394-0.804) by multivariate analysis in Asian. The HR value estimated for PFS was 0.526 (95 % CI 0.372-0.743) by univariate analysis and 0.437 (95 % CI 0.356-0.537) by multivariate analysis in Caucasian. The HR value estimated for PFS was 0.132 (95 % CI 0.006-3.027) by multivariate analysis in Asian. This data revealed that GBM patients with MGMT promoter methylation had longer OS and PFS by univariate or multivariate analysis in Caucasian regardless of therapeutic intervention. However, GBM patients with MGMT promoter methylation only had longer OS by multivariate analysis in Asian.

Cytotoxic T lymphocyte antigen 4 (CTLA-4) genetic polymorphisms are implicated to be associated with susceptibility to bone sarcomas, but published studies have reported inconclusive results. The objective of our study was to conduct a meta-analysis investigating the associations between CTLA-4 gene polymorphisms and risk of bone sarcomas. PubMed and Embase databases were searched for all articles published up to June 2, 2013. Odds ratio (OR) with a 95 % confidence interval (95 % CI) was used to assess the association. Finally, 11 individual studies with a total of 2,951 cases with bone sarcomas and 3,396 controls were included in the meta-analysis. There were four studies on the CTLA-4 49G/A polymorphism, three studies on CTLA-4 318C/T polymorphism, two studies on CTLA-4 1661A/G polymorphism, and two studies on CTLA-4 60A/G polymorphism. Overall, CTLA-4 49G/A polymorphism was obviously associated with risk of bone sarcomas (A vs. G: OR = 1.36, 95 % CI = 1.20-1.54; AA vs. GG: OR = 2.24, 95 % CI = 1.67-2.99; AA vs.

Runt-related transcription factor 3 (RUNX3) is a member of the runt-domain family of transcription factors. Emerging evidence indicates that RUNX3 is a tumor suppressor gene in several types of human cancers including esophageal cancer. However, the association between RUNX3 promoter methylation and esophageal cancer remains unclear. Here we conducted a systematic review and meta-analysis to quantitatively evaluate the effects of RUNX3 promoter methylation on the incidence of esophageal cancer.

Growing bodies of studies have investigated the associations between three progesterone receptor (PGR) polymorphisms, +331G/A, Alu insertion and Val660Leu, and susceptibility to ovarian cancer, but the results remain controversial and inconclusive. Thus, we conducted a meta-analysis to derive a more precise estimation of the associations.

Gliomas are the most common type of primary brain tumors. The XRCC1 Arg194Trp variant affects the proliferating cell nuclear antigen( PCNA) binding region, which suggests that this mutation may contribute to gliomagenesis and a number of articles have examine the association between XRCC1 Arg194Trp and the susceptibility to glioma. However, the results were conflicting. Test of heterogeneity, sensitivity analysis, meta- analysis, and assessment of publication bias were all performed in our present meta-analysis, covering a total of 5,407 patients and 7,715 healthy persons. In the overall analysis the XRCC1 Arg194Trp polymorphism showed a significant association with glioma susceptibility in a recessive mode l(for TrpTrp vs ArgArg+ArgTrp: OR=1.918, 95%CI=1.575-2.336, I2=2.3%). In addition, analysis of subgroups presented an increased risk in Asians and populations-based on hospitals. The results suggested that the XRCC1 Arg194Trp polymorphism is a genetic risk factor for glioma, especially in Asian population. To further evaluate gene-gene and gene-environment interactions on XRCC1 polymorphisms and glioma risk, thousands of subjects and tissue-specific biochemical characterizations are required.

MicroRNAs (miRNAs) act as tumor suppressors or promoters in neoplasia by regulating relative gene expression. The association between a single nucleotide polymorphism (SNP) rs4938723 in miR-34b/c and susceptibility to cancers was inconsistent in previous studies. In this study, we conducted a literature search of PubMed, Web of Science and Embase to identify all relevant studies in this meta-analysis with 6,036 cases and 6,204 controls. We found that the miR-34b/c rs4938723 polymorphism was significantly associated with increased risk of cancers in the heterozygous model (TC versus TT, OR=1.09, 95% CI=1.01-1.18, P=0.02). Subgroup analysis also revealed increased risk for Asian ethnicity in the heterozygous model (TC versus TT, OR=1.12, 95% CI=1.02-1.22, P=0.02), but decreased risk of colorectal cancer in homozygote model (CC versus TT, OR=0.66, 95% CI=0.47-0.92, P=0.02) and in the recessive model (CC versus TC+TT, OR=0.67, 95% CI=0.48-0.93, P=0.02) by cancer type. The current meta-analysis indicated that the miR-34b/c rs4938723 polymorphism may decrease susceptibility to colorectal cancer. Well-designed studies with larger sample size are required to further validate the results.