The impact of the Oncotype Dx (ODX) breast cancer assay on adjuvant chemotherapy (ACT) treatment decisions has been evaluated in many previous studies. However, it can be difficult to interpret the collective findings, which were conducted in diverse settings with limited sample sizes. We conducted a systematic review and meta-analysis to synthesize the results and provide insights about ODX utility. Studies, identified from PubMed, Embase, ASCO, and SABCS, were included if patients had ER+, node -, early-stage breast cancer, reported use of ODX to inform actual ACT decisions. Information was summarized and pooled according to: (1) distribution of ODX recurrence scores (RS), (2) impact of ODX on ACT recommendations, (3) impact of ODX on ACT use, and (4) proportion of patients following the treatment suggested by the ODX RS. A total of 23 studies met inclusion criteria. The distribution of RS categories was 48.8 % low, 39.0 % intermediate, and 12.2 % high (21 studies, 4,156 patients). ODX changed the clinical-pathological ACT recommendation in 33.4 % of patients (8 studies, 1,437 patients). In patients receiving ODX, receipt of ACT were: 28.2 % overall, 5.8 % low, 37.4 % intermediate, and 83.4 % high. Low RS patients were significantly more likely to follow the treatment suggested by ODX versus high RS patients RR: 1.07 (1.01–1.14) [corrected].The pooled results are consistent with most individual studies to date. The increased proportion of intermediate scores relative to original estimates may have implications for the clinical utility and cost impacts of testing. In addition, low versus high RS patients were significantly more likely to follow the ODX results, suggesting a tendency toward less aggressive treatment, despite a high ODX RS. Finally, there was a lack of studies on the impact of ODX on ACT use versus standard approaches, suggesting that additional studies are warranted.

Many studies have reported the role of xeroderma pigmentosum group D (XPD) with prostate cancer risk, but the results remained controversial. To derive a more precise estimation of the relationship, a meta-analysis was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between XPD Asp312Asn and Lys751Gln polymorphisms and prostate cancer risk. A total of 8 studies including 2620 cases and 3225 controls described Asp312Asn genotypes, among which 10 articles involving 3230 cases and 3582 controls described Lys751Gln genotypes and were also involved in this meta-analysis. When all the eligible studies were pooled into this meta-analysis, a significant association between prostate cancer risk and XPD Asp312Asn polymorphism was found. For Asp312Asn polymorphism, in the stratified analysis by ethnicity and source of controls, prostate cancer risk was observed in co-dominant, dominant and recessive models, while no evidence of any associations of XPD Lys751Gln polymorphism with prostate cancer was found in the overall or subgroup analyses. Our meta-analysis supports that the XPD Asp312Asn polymorphism contributed to the risk of prostate cancer from currently available evidence. However, a study with a larger sample size is needed to further evaluate gene-environment interaction on XPD Asp312Asn and Lys751Gln polymorphisms and prostate cancer risk.

The Ser326Cys polymorphism in the human 8-oxogunaine glycosylase (hOGG1) gene with lung cancer susceptibility had been investigated, but results were inconsistent and underpowered. The aim of this study was to conduct a meta-analysis assessing the association of hOGG1 Ser326Cys polymorphism with risk of lung cancer.

Numerous studies have investigated the risk of cancer associated with the polymorphism of epidermal growth factor (EGF) 61A>G, but results have been inconsistent. We performed this meta-analysis to drive a more precise estimation of the association between this polymorphism and risk of glioma. A comprehensive search was conducted to identify all case-control studies on the EGF +61A>G polymorphism and glioma risk. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to assess the strength of the association. Statistical analysis was performed with the software program Stata (version 12.0). A total of ten eligible studies, including 1,888 cases and 2,836 controls were included in this work. Overall, there was a significant association between EGF +61A>G polymorphism and glioma risk in the allele model (OR = 1.419, 95% CI = 1.144-1.759, P = 0.001). In the subgroup analysis by ethnicity, significant associations were also found in Asian populations under all different genetic models (homozygote model: OR = 1.727, 95% CI = 1.310-2.275, P = 0.000; heterozygote model: OR = 1.202, 95% CI = 1.023-1.413, P = 0.025; dominant model: OR = 1.279, 95% CI = 1.096-1.491, P = 0.002; recessive model: OR = 1.590, 95% CI = 1.221-2.070, P = 0.001; and A-allele versus G-allele OR = 1.600, 95% CI = 1.145-2.236, P = 0.006). However, no significant associations were found among Caucasians in all comparison models. In conclusion, the results suggest that there is a significant association between EGF +61A>G polymorphism and glioma risk among Asians.

Somatic DNA methyl transferase 3A (DNMT3A) mutations have been recognized recently as recurrent molecular aberrations in acute myeloid leukemia (AML). The precise role of these mutations in leukemogenesis remains elusive but a number of studies have already been conducted to study their potential prognostic value in AML patients with variable results. We performed a meta-analysis on published data from over 4500 AML patients to provide robust evidence supporting DNMT3A mutation testing in clinical setting for AML patients. Our meta-analysis showed that DNMT3A mutations were associated with M4 and M5 AML subtypes. Those mutations conferred significantly worse prognosis with both shorter OS (p=0.0004) and shorter RFS (p=0.002). Notably, DNMT3A mutations appeared to be an independent adverse prognostic factor also in younger patients with normal cytogenetics AML (OS (p=0.01) and RFS (p=0.0005)) and also in the subgroup of patients with high risk genotypes defined according to the criteria of the European Leukemia Net (ELN) (OS (p=0.002)). Therefore, DNMT3A mutational status can improve the risk stratification of AML patients in the setting of integrated mutational profiling.

Inhibition of the phosphatidylinositol-3-kinase (PI3K) signaling pathway is a cancer treatment strategy that has entered into clinical trials. We performed a meta-analysis on the frequency of prominent genetic (PIK3CA mutation, PIK3CA amplification and PTEN deletion) and protein expression (high PI3K, PTEN loss and high pAkt) aberrations in the PI3K pathway in gastric cancer (GC) and colorectal cancer (CRC). We also performed laboratory analysis to investigate the co-occurrence of these aberrations. The meta-analysis indicated that East Asian and Caucasian GC patients differ significantly for the frequencies of PIK3CA Exon 9 and 20 mutations (7% vs. 15%, respectively), PTEN deletion (21% vs. 4%) and PTEN loss (47% vs. 78%), while CRC patients differed for PTEN loss (57% vs. 26%). High study heterogeneity (I(2) > 80) was observed for all aberrations except PIK3CA mutations. Laboratory analysis of tumors from East Asian patients revealed significant differences between GC (n = 79) and CRC (n = 116) for the frequencies of PIK3CA amplification (46% vs. 4%) and PTEN loss (54% vs. 78%). The incidence of GC cases with 0, 1, 2 and 3 concurrent aberrations was 14%, 52%, 27% and 8%, respectively, while for CRC it was 10%, 60%, 25% and 4%, respectively. Our study consolidates knowledge on the frequency, co-occurrence and clinical relevance of PI3K pathway aberrations in GC and CRC. Up to 86% of GC and 90% of CRC have at least one aberration in the PI3K pathway, and there are significant differences in the frequencies of these aberrations according to cancer type and ethnicity.

Genome-wide association studies have identified 6p21 as a new lung cancer susceptibility locus in populations of European descent. Since then, the relationship between common variations on 6p21 and lung cancer has been reported in various ethnic groups; however, these studies have yielded inconsistent results. To investigate this inconsistency, we performed a meta-analysis of 11 studies involving a total of 36,890 cases and 52,767 controls for three widely studies polymorphisms (rs4324798, rs3117582, and rs9295740) to evaluate its effect on genetic susceptibility for lung cancer. An overall random-effects per-allele odds ratio (OR) of 1.11 (95% confidence interval (CI) 1.04–1.19; P = 0.002) and 1.20 (95% CI 1.14–1.26; P < 10(−5)) was found for the rs4324798 and rs3117582 polymorphism, respectively. Marginal significant associations were also detected for rs9295740 with per-allele OR of 1.09 (95% CI 1.01–1.18; P = 0.03). In the subgroup analysis by ethnicity, significantly increased risks were found for the three polymorphisms among Caucasians. Similar results were also observed using dominant or recessive genetic models. This meta-analysis demonstrated that the three common variations (rs4324798, rs3117582, and rs9295740) on 6p21 are risk factors associated with increased lung cancer susceptibility, but these associations vary in different ethnic populations.

Cytovillin plays structural and regulatory roles in the assembly and stabilization of specialized plasma membrane domains and in the tumor angiogenesis. Cytovillin expression has been proposed to be an effective biomarker of prognosis in patients with osteosarcoma, and many studies have been performed to assess the prognostic role of cytovillin expression in patients with osteosarcoma. We performed this meta-analysis to provide a comprehensive evaluation of the role of cytovillin expression on the overall survival rate by calculating the pooled risk ratio (RR) with corresponding 95% confidence interval (95% CI). Finally, eight studies with a total of 415 patients with osteosarcoma were included into the meta-analysis. Meta-analysis of total eight studies showed that cytovillin expression was obviously associated with lower overall survival rate in patients with osteosarcoma (RR = 0.41, 95% CI 0.28–0.58, P < 0.001). Meta-analysis of five studies with large sample still showed that cytovillin expression was obviously associated with lower overall survival rate (RR = 0.48, 95% CI 0.38–0.60, P < 0.001). In conclusion, the meta-analysis shows that cytovillin expression is obviously associated with lower overall survival rate in patients with osteosarcoma, and it is an effective biomarker of prognosis.

Studies investigating the association between genetic polymorphism of glutathione S-transferase T1 (GSTT1) and hepatocellular carcinoma (HCC) risk have reported conflicting results. Therefore, we conducted this meta-analysis to provide more precise evidence. Databases including PubMed, Embase, SCOPUS, ISI Web of Science, and Wangfang were searched for relevant studies. Potential sources of heterogeneity were also assessed by subgroup analysis. Funnel plots and Egger's linear regression were used to test publication bias among the articles. Finally, a total of 28 studies involving 3,897 HCC patients and 6,117 controls were included in this meta-analysis. In a combined analysis, the summary odds ratio for HCC of the GSTT1 null genotype was 1.43 (95% confidence interval (CI) 1.22–1.68, P < 10(−5)). In the subgroup analysis by ethnicity, significantly increased risks were found in East Asians for GSTT1 null polymorphism, while no significant associations were found among Caucasian, South Asian, and African populations. When stratified by a source of controls, both population- and hospital-based studies get consistent positive results. By pooling data from 10 studies (1,639 cases and 2,224 controls) that considered combinations of GSTT1 and GSTM1 genotypes, a statistically significant increased risk for HCC (odd ratio = 1.85, 95% CI 1.37–2.49) was detected for individuals with combined deletion mutations in both genes compared with positive genotypes. No evidence of publication bias was observed. Our result suggests that the GSTT1 null genotype contributes to an increased risk of HCC in East Asians and that interaction between unfavorable GSTs genotypes may exist.

T-cell acute lymphoblastic leukemia (T-ALL) is a complex disease, resulting from proliferation of differentially arrested immature T cells. The molecular mechanisms and the genes involved in the generation of T-ALL remain largely undefined. In this study, we propose a set of genes to differentiate individuals with T-ALL from the nonleukemia/healthy ones and genes that are not differential themselves but interconnected with highly differentially expressed ones. We provide new suggestions for pathways involved in the cause of T-ALL and show that network-based classification techniques produce fewer genes with more meaningful and successful results than expression-based approaches. We have identified 19 significant subnetworks, containing 102 genes. The classification/prediction accuracies of subnetworks are considerably high, as high as 98%. Subnetworks contain 6 nondifferentially expressed genes, which could potentially participate in pathogenesis of T-ALL. Although these genes are not differential, they may serve as biomarkers if their loss/gain of function contributes to generation of T-ALL via SNPs. We conclude that transcription factors, zinc-ion-binding proteins, and tyrosine kinases are the important protein families to trigger T-ALL. These potential disease-causing genes in our subnetworks may serve as biomarkers, alternative to the traditional ones used for the diagnosis of T-ALL, and help understand the pathogenesis of the disease.

Previous studies have focused on the association of a gene (EPHX1) encoding microsomal epoxide hydrolase with the carcinogenesis of hepatocellular carcinoma (HCC). In the present study, we performed a meta-analysis to systematically summarize the possible association between EPHX1 genetic polymorphisms and the risk for HCC. We conducted a search of case-control studies on the associations of EPHX1 genetic polymorphisms with susceptibility to HCC in PubMed, EMBASE, ISI Web of Science, Wanfang database in China, and the Chinese National Knowledge Infrastructure databases. Data from eligible studies were extracted for meta-analysis. HCC risk associated with EPHX1 genetic polymorphism was estimated by pooled odds ratios and 95% confidence intervals. Thirteen studies were included in the present meta-analysis. Our results showed that, for the two polymorphisms (337 T > C and 416A > G) of EPHX1 gene, neither allele frequency nor genotype distributions were associated with risk for HCC in all genetic models (all P > 0.05). This meta-analysis suggests that EPHX1 genetic polymorphisms were not associated with the risk of HCC.

Study results on the association between RAD51 gene -135G/C polymorphism and risk of myelodysplastic syndrome (MDS) or acute leukemia are inconsistent. A meta-analysis was conducted to identify the association. A systematic search was performed in PubMed, Embase, CNKI, VIP, Wanfang databases to collect all relevant studies until January 2013. Meta-analysis was carried out using fixed/random model by Review Manager 5.1 and STATA10.0. A total of 10 eligible studies with 2,656 patients and 3,725 controls were included in meta-analysis. Significant association was detected between -135G/C polymorphism and increased MDS risk (CC + GC vs. GG: OR = 1.46, 95% CI = 1.11-1.92; CC vs. GC + GG: OR = 2.45, 95% CI = 1.23-4.89), while no association was observed for acute leukemia. Subgroup analysis by subtypes of acute leukemia and ethnicity showed no significant results either. Our meta-analysis indicated that the -135G/C polymorphism might be associated with increased susceptibility of MDS. However, lack of evidence supported association of this polymorphism with acute leukemia. Additional well-designed studies with larger samples are required to verify our results.

The epidermal growth factor receptor (EGFR) plays important roles in the development of gastric cancer. This study aims to analyze the prognostic value of EGFR in patients with gastric cancer.

The transcription factor 7-like 2 (TCF7L2) gene has been suggested to play an important role in the pathogenesis of cancer. However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the associations between TCF7L2 polymorphism and cancer risk.

Mothers against decapentaplegic homolog 7 (SMAD7) rs12953717 polymorphism has been implicated to alter the risk of colorectal cancer (CRC), but the results are controversial. The objective of this study was to quantitatively evaluate the association between SMAD7 rs12953717 polymorphism and CRC susceptibility. A comprehensive search was conducted to identify all eligible studies of SMAD7 rs12953717 polymorphism and CRC risk. Pooled odds ratio and 95% confidence interval were calculated using a fixed or random effects model. Statistical analysis was performed with Review Manager 5.0 and Stata 11. A total of 11 case-control studies, including 12,058 cases and 11,444 controls, were identified. The combined results based on all studies suggested that rs12953717 was associated with CRC risk under all genetic models. When stratifying for race, the data showed that the rs12953717 was associated with a significantly increased CRC risk under all genetic models in Caucasians. Statistically significant association was found in all genetic models except in recessive model comparison in the subgroup of Asians. After stratifying the studies by study design, there was a significant association between rs12953717 polymorphism and CRC risk under all genetic models in the subgroup of population-based studies. Our study suggests that rs12953717 polymorphism is associated with an increased CRC risk.

Glutathione S-transferase T1 (GSTT1) null genotype has been proven to be associated with risks of many cancers. There were also many studies assessing on the association between GSTT1 null genotype and nasopharyngeal carcinoma risk in Chinese, but the findings from those studies were inconsistent. We performed a meta-analysis to provide a more precise assessment on the effect of GSTT1 null genotype on nasopharyngeal carcinoma risk. The PubMed and Wanfang databases were searched to identify eligible case-control studies on the association between GSTT1 null genotype and risk of nasopharyngeal carcinoma in Chinese. The pooled odds ratios (OR) with corresponding 95% confidence intervals (95% CI) were used to assess the association. Eight case-control studies with a total of 3,702 individuals were finally included in the meta-analysis. Meta-analysis of a total of eight studies showed that GSTT1 null genotype was significantly associated with increased risk of nasopharyngeal carcinoma in Chinese (OR = 2.27; 95% CI 1.41-3.67; P = 0.001). The finding from cumulative meta-analysis showed that there was a trend of more obvious association between GSTT1 null genotype and risk of nasopharyngeal carcinoma in Chinese as data accumulated by publication year. Therefore, the GSTT1 null genotype is significantly associated with increased risk of nasopharyngeal carcinoma in Chinese.

Survivin has been implicated as a potential prognostic marker in a wide range of malignant tumours. However, the prognostic impact of survivin in gastric cancer remains to be controversial and published data are sometimes heterogeneous. Thus, aim of this study was to review the literature by performing an electronical database search via PubMed and EMBASE to identify eligible studies that assessed the impact of survivin as prognostic marker and its association with clinicopathological variables. Database search until November 21st 2012 retrieved 20 studies comprising 2,695 gastric cancer patients that assessed expression of survivin by immunohistochemistry or RT-PCR analyses in gastric cancer specimens. Meta-analyses of clinicopathological variables revealed an association between the expression of survivin and the presence of lymph node metastases (pooled OR: 0.58; 95 % CI 0.35-0.96). In addition, a correlation between the expression of survivin and overall survival for patients with gastric cancer (pooled HR 1.93; 95 % CI 1.51-2.48) became evident. More importantly, we were able to exclude a severe heterogeneity (I(2) = 31 %) or publication bias for the survival analyses. Furthermore, one-way sensitivity analysis and subgroup analyses regarding the method used to detect survivin, the type of survival analysis, the study quality and whether information was provided regarding neoadjuvant therapy supported our initial results. In conclusion, this meta-analysis indicates the prognostic significance of survivin in patients with gastric cancer.

In the past two decades, approximately 1000 reports have been published regarding associations between genetic variants in candidate genes and risk of colorectal cancer (CRC). Study results are inconsistent. We aim to provide a synopsis of the current understanding of genetic factors for CRC risk through systematically evaluating results from previous studies.

There is a possible association between myeloperoxidase (MPO) 463G>A polymorphism and risk of lung cancer, but previous studies report conflicting results. We performed a meta-analysis of available molecular epidemiologic studies to comprehensively assess the association between MPO 463G>A polymorphism and risk of lung cancer. A systemic literature search was performed in Pubmed, Embase, and Wanfang databases for molecular epidemiologic studies on the association MPO 463G>A polymorphism and risk of lung cancer on March 16, 2013. The pooled odds ratios (ORs) with their 95% confidence interval (95% CI) were calculated to assess the strength of the association. Twenty-six individual case-control studies with a total of 18,433 subjects (7,752 cases and 10,681 controls) were finally included into the meta-analysis. Overall, MPO 463G>A polymorphism was significantly associated with decreased risk of lung cancer under two main genetic comparison models (for A versus G, OR = 0.91, 95 % CI 0.83-0.99, P = 0.035; for AG/AA versus GG, OR = 0.90, 95% CI 0.81-0.99, P = 0.029). Meta-analysis of studies with high quality also showed that MPO 463G>A polymorphism was significantly associated with decreased risk of lung cancer under two main genetic comparison models (for A versus G, OR = 0.91, 95% CI 0.83-0.99, P = 0.035; for AG/AA versus GG, OR = 0.90, 95% CI 0.80-0.99, P = 0.048). Subgroup analysis by ethnicity further showed that there was a significant association between MPO 463G>A polymorphism and decreased risk of lung cancer in Caucasians but not in Asians. The meta-analysis suggests that MPO 463G>A polymorphism is associated with decreased risk of lung cancer, especially in Caucasians.

Many epidemiologic studies have investigated the association between myeloperoxidase (MPO) G-463A polymorphism and lung cancer risk, but the results were controversial. We performed a meta-analysis of 25 studies on MPO polymorphism and lung cancer risk published before July 2013. The allele of A was found to be associated with decreased risk of lung cancer compared with G allele (OR, 0.90; 95% CI, 0.82-0.98) in the general population. The significant association remained in the comparison between AA + AG and GG (OR, 0.92; 95% CI, 0.87-0.98). When it was stratified according to Asian population, the association between MPO polymorphism and lung cancer risk was further strengthened. However, no associations were found in the Caucasian population. This meta-analysis has demonstrated that MPO polymorphism might contribute to individual's susceptibility to lung cancer in Asian population. Caucasian authors could re-investigate the association between MPO polymorphism and lung cancer risk with more specific participants. Future studies focusing on interactions between combined genes and environmental risk factors are warranted.