FAS is a cell surface receptor involved in apoptotic signaling in many cell types including cells of the immune system. The -1377 A/G polymorphism of FAS gene has been detected in breast cancer. However, the published evidence regarding the -1377 A/G polymorphism and breast cancer risk has generated controversial results. We performed a meta-analysis of five case-control association studies totaling to 5,995 study subjects including 2,905 cases and 3,090 controls. The combined odd ratios (ORs) with its 95% CIs were used to assess the association of the -1377 A/G polymorphism correlated with breast cancer susceptibility with the fixed-effects model. The combined results showed significantly increased risk associated with the -1377 A/G polymorphism under AA vs. GG genetic model (OR = 1.28, 95% CI = 1.04-1.58; heterogeneity test: P = 0.614, I (2)  = 0.0%), AA vs. GA + GG genetic model (OR = 1.24, 95 CI = 1.02-1.51; heterogeneity test: P = 0.349, I (2)  = 10.0%), and allele model A vs. G (OR = 1.10, 95%CI = 1.02-1.20; heterogeneity test: P = 0.422, I (2)  = 0.0%). Similarly, significant association was found in Asians. In stratified analyses by control source, a higher risk was indicated in the hospital-based studies rather than the population-based studies. This meta-analysis suggests that the -1377 A/G polymorphism is likely to be associated with the risk of breast cancer, especially the A allele in Asians.

Differential gene expression analysis between healthy and diseased groups is a widely used approach to understand the molecular underpinnings of disease. A wide variety of experimental and bioinformatics techniques are available for this type of analysis, yet their impact on the reliability of the results has not been systematically studied. We performed a large scale comparative analysis of clinical expression data, using several background corrections and differential expression metrics. The agreement between studies was analyzed for study pairs of same cancer type, of different cancer types, and between cancer and non-cancer studies. We also replicated the analysis using differential coexpression. We found that agreement of differential expression is primarily dictated by the microarray platform, while differential coexpression requires large sample sizes. Two studies using different differential expression metrics may show no agreement, even if they agree strongly using the same metric. Our analysis provides practical recommendations for gene (co)expression analysis.

Numerous studies have investigated the risk of colorectal cancer (CRC) associated with the polymorphism of DNA methyltransferase 3B (DNMT3B) 149 C>T, 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 CRC. A comprehensive search was conducted to identify all case-control studies of the -149C>T polymorphism of DNMT3B and CRC risk. A total of seven eligible studies, including 2,666 cases and 4,022 controls, relating the DNMT3B polymorphism of -149C>T to the risk of CRC were identified. It suggested no significant associations between -149C>T polymorphism of DNMT3B gene and the risk of developing CRC in the recessive, dominant, and co-dominant models (for CC versus TT: OR = 0.90, 95% CI = 0.90-1.25, P heterogeneity = 0.37; for recessive model: OR = 0.54, 95% CI = 0.28-1.04, P heterogeneity = 0.00001; for dominant model: OR = 1.07, 95% CI = 0.93-1.23, P heterogeneity = 0.83; and for C allele versus T allele: OR = 0.70, 95% CI = 0.43-1.13, P heterogeneity = 0.00001). In the subgroup analysis, there is no significant associations were also found in European populations (for CC versus TT: OR = 1.09, 95% CI = 0.92-1.30, P heterogeneity = 0.88; for recessive model: OR = 1.00, 95% CI = 0.88-1.13, P heterogeneity = 0.14; for dominant model: OR = 1.50, 95% CI = 0.89-2.54, P heterogeneity = 0.00001; and for C allele versus T allele: OR = 0.70, 95% CI = 0.38-1.28, P heterogeneity = 0.00001). In conclusion, no significant association was found between the -149C>T polymorphisms in DNMT3B and CRC susceptibility.

Prostate cancer (PCa) is a malignant disease influencing numerous men worldwide every year. However, the exact pathogenesis and the genes, environment, and other factors involved have not been explained clearly. Some studies have proposed that cell signaling pathways might play a key role in the development and progression of PCa. According to our previous study, the RTK/ERK pathway containing nearly 40 genes was associated with PCa risk. On the basis of these genes, we conducted a meta-analysis with our own Chinese Consortium for Prostate Cancer Genetics (ChinaPCa) study and available studies in the databases to describe the association between the pathway and PCa on the SNP level. The results suggested that rs4764695/IGF1 (recessive model: pooled OR=0.92, 95%CI=0.852-0.994, P=0.034; I(2)=0%, P=0.042; allele analysis: pooled OR=0.915, 95%CI=0.874-0.958, P=0; I(2)=0%, P=0.424; codominant model: OR=0.835, 95%CI=0.762-0.916, P=0; I(2)=0%, P=0.684) and rs1570360/VEGF (recessive model: OR=0.596, 95%CI=0.421-0.843, P=0.003; I(2)=23.9%, P=0.269; codominant model: OR=0.576, 95%CI=0.404-0.820, P=0.002; I(2)=49.1%, P=0.140) were significantly associated with PCa. In subgroup analysis, the relationship was also found in Caucasians for IGF1 (dominant model: OR=0.834, 95%CI=0.769-0.904, P=0; allele analysis: OR=0.908, 95%CI=0.863-0.955, P=0; AA vs CC: OR=0.829, 95%CI=0.750-0.916, P=0; AC vs CC: OR=0.837, 95%CI=0.768-0.912, P=0). In addition, in Asians (allele analysis: OR=0.21, 95%CI=0.168-0.262, P=0) and Caucasians (recessive model: OR=0.453, 95%CI: 0.240-0.855, P=0.015; codominant model: OR=0.464, 95%CI=0.240-0.898, P=0.023) for VEGF, the association was significant. The results indicated that rs4764695/IGF1 and rs1570360/VEGF might play a key role in the development and progression of PCa. On the SNP level, we suggest that the study gives us a new view of gene-pathway analysis and targeted therapy for PCa.

Genetic variations in DNA repair genes are thought to modify DNA repair capacity and may to be related to cancer susceptibility. However, epidemiological study results have been inconsistent. In this meta-analysis, we assessed 24 case-control studies of association between the X-ray repair cross complementing group 1 (XRCC1) Arg399Gln polymorphism and bladder cancer susceptibility in the general population and in Asian and non-Asian subgroups. A moderately significant association with bladder cancer risk was found for AG vs GG (OR=1.110, 95% CI=1.018-1.210). No significant associations with bladder cancer risk were found for AA vs GG (OR=0.942, 95% CI=0.823-1.077), the dominant model AA/AG vs GG (OR=1.075, 95% CI=0.990-1.167) and the recessive model AA vs AG/GG(OR=0.890, 95% CI=0.788-1.005). In subgroup analysis, a moderately significant association was also found for AG vs GG (OR=1.091, 95% CI=1.008-1.180) in non-Asian subgroup. The analysis suggests that the XRCC1 Arg399Gln polymorphism might be a moderate risk factor for bladder cancer, especially in non-Asian population.

A functional polymorphism in the NQO1 gene, featuring a 609C>T substitution,leading to proline to serine amino-acid and enzyme activity changes, has been implicated in cancer risk. However, individually published investigations showed inconclusive results, especially for leukemia. In this study, we therefore performed a meta- analysis of 21 publications with a total of 3,634 cases and 4,827controls, mainly for leukemia. We summarized the data on the association between the NQO1 609C>T polymorphism and risk of leukemia and performed subgroup analyses by ethnicity and leukemia type. We found that the variant TT homozygous genotype o was associated with a modestly increased risk of leukemia (TT versus CT/CC: OR = 1.23, 95%CI = 1.00 - 1.51, heterogeneity = 0.76; I2 = 0%). Following further stratified analyses, increased risk was only observed in subgroups of Caucasians. This meta-analysis suggests that the NQO1 609T allele is a high-penetrance risk factor for leukemia in Caucasians. The effect on leukemia may be modified by ethnicity and leukemia type, and the small sample sizes of the subgroup analyses suggest that further larger studies are needed.

Fine-needle aspiration (FNA) is routinely used in the preoperative evaluation of thyroid nodules. However, approximately 5-20% of thyroid nodules are considered indeterminate or suspicious cases that do not meet clinical standards. The B-RAF(V600E) mutation has been reported in FNA specimens. We conducted a systematic review to evaluate the diagnostic value of testing for B-RAF(V600E) in thyroid nodules that are difficult to diagnose by FNA. A systematic literature search was performed from January 1, 2002 to June 30, 2012. Articles were obtained by searching two electronic databases (MEDLINE and EMBASE), hand searching selected journals, and contacting authors. Article quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Sensitivity, specificity, and other measures of accuracy were pooled using random effects models. Summary receiver operating characteristic (SROC) curves were used to summarize overall diagnostic accuracy. A total of 16 studies incorporating 1131 patients were included in a meta-analysis on diagnostic accuracy of B-RAF(V600E) tests. Pooled sensitivity was 0.60 (95% confidence interval [CI]: 0.556-0.634), pooled specificity was 0.99 (95% CI 0.976-0.997), and the area under the curve of the SROC curve was 0.8376. Q index value was 0.7696. Our data suggest a potentially useful adjunct to evaluating thyroid nodules that are difficult to diagnose. The B-RAF(V600E) test has a high positive predictive value and could help clinicians formulate a more individualized treatment schedule. When supplemented with other noninvasive test methods, the B-RAF(V600E) test could be a powerful adjunct with extensive clinical applications.

Next-generation sequencing technologies have led to profound characterization of mutation spectra for several cancer types. Hence, we sought to systematically compare genomic aberrations between primary tumors and cancer lines. For this, we compiled publically available sequencing data of 1651 genes across 905 cell lines. We used them to characterize 23 distinct primary tumor sites by a novel approach that is based on Bayesian spam-filtering techniques. Thereby, we confirmed the strong overall similarity of alterations between patient samples and cell culture. However, we also identified several suspicious mutations, which had not been associated with their cancer types before. Based on these characterizations, we developed the inferring cancer origins from mutation spectra (ICOMS) tool. On our cell line collection, the algorithm reached a prediction specificity rate of 79%, which strongly variegated between primary cancer sites. On an independent validation cohort of 431 primary tumor samples, we observed a similar accuracy of 71%. Additionally, we found that ICOMS could be employed to deduce further attributes from mutation spectra, including sub-histology and compound sensitivity. Thus, thorough classification of site-specific mutation spectra for cell lines may decipher further genome-phenotype associations in cancer.

The association between the epidermal growth factor receptor (EGFR) 142285G > A polymorphism and the susceptibility to breast cancer is unclear. We conducted a meta-analysis of all published studies to estimate the association of EGFR 142285G > A polymorphism and breast cancer risk. Systematic computerized searching of the PubMed, Web of Science, and Wanfang databases was performed for relevant publications. Overall, there were three eligible case-control studies with 1,360 cases and 1,522 controls included into our study. The pooled ORs showed that the EGFR 142285G > A variant genotypes did not increase or decrease the risk of breast cancer under the following gene models: A vs. G, OR = 1.07, 95% CI 0.96-1.19, P OR = 0.240; AA vs. GG, OR = 1.14, 95% CI 0.91-1.42, P OR = 0.239; GA vs. GG, OR = 0.99, 95% CI 0.83-1.17, P OR = 0.892; GA + AA vs. GG, OR = 1.03, 95% CI 0.87-1.21, P OR = 0.727; AA vs. GG + GA, OR = 1.17, 95% CI 0.97-1.42, P OR = 0.096. The between-study heterogeneity was not significant among all studies. The current meta-analysis showed no evidence for significant association between EGFR 142285G > A polymorphism and breast cancer risk. Subsequent studies with large sample size are needed for further elucidation.

Chronic infection of viral hepatitis is the main cause of liver cancer. There were many studies assessing the associations of methylenetetrahydrofolate reductase (MTHFR) Ala222Val polymorphism with risks of hepatitis and hepatitis-related liver cancer, but no consistent results were reported. To investigate the associations of MTHFR Ala222Val polymorphism with risks of hepatitis and hepatitis-related liver cancer, we performed a meta-analysis of published case-control studies. Eligible studies were searched from PubMed and Chinese National Knowledge Infrastructure (CNKI) databases. The odds ratio (OR) and corresponding 95 % confidence interval (95 %CI) were used to assess the associations. Twenty-one individual studies with a total of 8,187 subjects were included. Overall, MTHFR Ala222Val polymorphism was not significantly associated with risks of liver cancer, hepatitis-related liver cancer, and non-hepatitis-related liver cancer. However, MTHFR Ala222Val polymorphism was significantly associated with risk of hepatitis infection (Val vs. Ala: OR = 1.15, 95 %CI 1.01-1.32, P = 0.03; ValVal/AlaVal vs. AlaAla: OR = 1.37, 95 %CI 1.11-1.68, P = 0.003). Therefore, MTHFR Ala222Val polymorphism is significantly associated with risk of hepatitis infection but not liver cancer. More studies are needed to further assess the association between MTHFR Ala222Val polymorphism and hepatitis-related liver cancer.

The objective of this study was to summarize all clinical studies evaluating the prognostic role of gemcitabine (GEM) metabolic genes in pancreaticobiliary (PB) cancer patients receiving GEM therapy in the neoadjuvant, adjuvant, or palliative settings.

In addition to HLA, recent genome-wide association studies (GWASs) of Hodgkin's lymphoma (HL) have identified susceptibility loci for HL at 2p16.1, 8q24.21 and 10p14. In this study, we perform a GWAS meta-analysis with published GWAS (totalling 1,465 cases and 6,417 controls of European background), and follow-up the most significant association signals in 2,024 cases and 1,853 controls. A combined analysis identifies new HL susceptibility loci mapping to 3p24.1 (rs3806624; P=1.14 × 10(-12), odds ratio (OR)=1.26) and 6q23.3 (rs7745098; P=3.42 × 10(-9), OR=1.21). rs3806624 localizes 5' to the EOMES (eomesodermin) gene within a p53 response element affecting p53 binding. rs7745098 maps intergenic to HBS1L and MYB, a region previously associated with haematopoiesis. These findings provide further insight into the genetic and biological basis of inherited susceptibility to HL.

The Bcl-2-associated X protein (Bax) is a proapoptotic member of the Bcl-2 family known to be activated and upregulated during apoptosis. Single nucleotide polymorphisms (SNPs) in Bax promoter may participate in the process of carcinogenesis by altering its own expression and the cancer related genes. Bax-248G>A polymorphism has been implicated to alter the risk of cancer, but the listed results are inconsistent and inconclusive. In the present study, we performed a meta-analysis to systematically summarize the possible association of this polymorphism with the risk of cancer.

Numerous epidemiological studies have examined associations of genetic variations in LEP (G2548A, -2548 nucleotide upstream of the ATG start site) and LEPR (Q223R, nonsynonymous SNP in exon 6) with cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis to comprehensively evaluate such associations.

The association between the polymorphism of catechol-O-methyltransferase (COMT) Val158Met and breast cancer risk is still inconclusive. We performed a meta-analysis to derive a more precise estimation of the relationship. A total of 18 studies including 5,175 cases and 6,463 controls were involved in this meta-analysis. When all studies were pooled into the meta-analysis, no significantly elevated breast cancer risk was associated with all genetic models (for additive model: OR = 1.273, 95% CI = 0.947-1.711, P heterogeneity = 0.000; P = 0.110; for dominant model: OR = 1.080, 95% CI = 0.945-1.234, P heterogeneity = 0.001; P = 0.259; for recessive model: OR = 1.242, 95% CI = 0.941-1.641, P heterogeneity = 0.000; P = 0.126; for allele comparison model: OR = 1.096, 95% CI = 0.976-1.230, P heterogeneity = 0.000; P = 0.121). In the subgroup analysis by controls source, the same results were found in all genetic models. In summary, this meta-analysis suggests that the COMT Val158Met polymorphism is not a risk factor for breast cancer development. However, large sample and representative population-based studies with homogeneous breast cancer patients and well-matched controls are warranted to confirm this finding.

Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol-anchored 123-amino acid protein related to the cell proliferation inhibition and/or cell death induction activity which has attracted considerable attention as a candidate gene for gastric cancer (GC) since it was first identified through genome-wide association approach. Since then, the relationship between PSCA polymorphisms (rs2294008, rs2976392) and GC has been reported in various ethnic groups; however, these studies have yielded inconsistent results. To investigate this inconsistency, we performed a meta-analysis of 16 studies involving a total of 18,820 cases and 35,756 controls for the two widely studied polymorphisms of PSCA on genetic susceptibility for GC. Overall, the summary odds ratio for GC was 1.46 (95% CI 1.30-1.69, P < 10(-5)) and 1.49 (95% CI 1.22-1.82, P < 10(-4)) for PSCA rs2294008 and rs2976392 polymorphisms, respectively. Meanwhile, haplotype analyses of the two polymorphisms revealed a significant association between the combination of these alleles and GC risk. When stratifying for ethnicity, significantly increased risks were found for rs2294008 and rs2976392 polymorphism among East Asians in all genetic models, while no significant associations were observed for the rs2294008 polymorphism in Caucasians. In the stratified analyses according to histological type, and source of controls, evidence of gene-disease association was still obtained. In addition, our data indicate that rs2294008 of PSCA is involved in GC susceptibility and confer its effect primarily in noncardia tumors (OR = 1.30, 95% CI 1.12-1.53, P < 10(-4)). Our findings demonstrated that rs2294008 and rs2976392 polymorphism of PSCA is a risk-conferring factor associated with increased GC susceptibility, especially in East Asians.

Many studies have reported the role of methylenetetrahydrofolate reductase (MTHFR) gene Ala222Val polymorphism with ovary 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 MTHFR Ala222Val polymorphism and ovary cancer risk. A total of 8 studies including 3,723 cases and 4,001 controls were also involved in this meta-analysis. When all the eligible studies were pooled into this meta-analysis, no significant association between ovary cancer risk and MTHFR Ala222Val polymorphism was found in all genetic models [codominant model: OR = 0.980, 95% CI = 0.756-1.270, P h = 0.088, P = 0.877; dominant model: OR = 1.022, 95% CI = 0.864-1.208, P h = 0.033, P = 0.803; recessive model: OR = 1.050, 95% CI = 0.803-1.373, P h = 0.032, P = 0.723; allele comparison model: OR = 1.028, 95% CI = 0.898-1.178, P h = 0.012, P = 0.685]. In the stratified analysis by ethnicity, no evidence of any associations of this polymorphism with ovary cancer was found in the Caucasian populations. Our meta-analysis supports that the MTHFR Ala222Val polymorphism is not contributed to the risk of ovary cancer from currently available evidence.

Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis in the process of tumor growth and metastasis. In present study, we conducted a case-control study and meta-analysis to evaluate the genetic effects of VEGF -634G/C and VEGF -2578C/A polymorphisms and risk of lung cancer. A total of 175 subjects were recruited for case-control study and seven studies were included in the meta-analysis. Our case-control study showed that VEGF -634G/C polymorphism had no association with lung cancer risk (CC vs. GG: OR = 0.88, 95% CI = 0.37-2.11), whereas there was an association between VEGF -2578CC genotype and decrease in lung cancer risk (CC vs.

To estimate the risks of ovarian cancer and breast cancer associated with oral contraceptive (OC) use among women at elevated risk owing to mutations in BRCA1/2 or a strong family history.

Methylenetetrahydrofolate reductase (MTHFR) has been implicated in lung cancer risk and response to platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). However, the results are controversial. We performed meta-analysis to investigate the effect of MTHFR C677T polymorphism on lung cancer risk and response to platinum-based chemotherapy in advanced NSCLC.