Previous reports implicate CYP2E1 RsaI/PstI polymorphism as a possible risk factor for several cancers. Published studies on the relationship of CYP2E1 RsaI/PstI polymorphisms with the susceptibility to gastric cancer are controversial. This study aimed to determine this relationship accurately.

More than 20 million archival tissue samples are stored annually in the United States as formalin-fixed, paraffin-embedded (FFPE) blocks, but RNA degradation during fixation and storage has prevented their use for transcriptional profiling. New and highly sensitive assays for whole-transcriptome microarray analysis of FFPE tissues are now available, but resulting data include noise and variability for which previous expression array methods are inadequate.

Tumor-specific antigens (TSA) are central elements in the immune control of cancers. To systematically explore the TSA genome, we developed a computational technology called heterogeneous expression profile analysis (HEPA), which can identify genes relatively uniquely expressed in cancer cells in contrast to normal somatic tissues. Rating human genes by their HEPA score enriched for clinically useful TSA genes, nominating candidate targets whose tumor-specific expression was verified by reverse transcription PCR (RT-PCR). Coupled with HEPA, we designed a novel assay termed protein A/G-based reverse serological evaluation (PARSE) for quick detection of serum autoantibodies against an array of putative TSA genes. Remarkably, highly tumor-specific autoantibody responses against seven candidate targets were detected in 4% to 11% of patients, resulting in distinctive autoantibody signatures in lung and stomach cancers. Interrogation of a larger cohort of 149 patients and 123 healthy individuals validated the predictive value of the autoantibody signature for lung cancer. Together, our results establish an integrated technology to uncover a cancer-specific antigen genome offering a reservoir of novel immunologic and clinical targets.

Glioma is one of the most common tumors of the central nervous system, and one of its main types is astrocytoma. Microarray technology has been widely used to explore the molecular mechanism of cancer. It is universally accepted that meta-analysis considerably improves the statistical robustness of results, particularly in clinical research. To obtain the maximum reliability, we used three different meta-analyses to integrate the four microarray datasets, GSE16011, GSE4290, GSE2223, and GSE19728 (local), and defined the common differentially expressed genes (DEGs) in astrocytomas compared with normal brain tissue. Four DEGs, PCNA, CDC2, CDK2 and CCNB2, which are components of the cell cycle pathway, were chosen for Real-Time Polymerase Chain Reaction (RT-PCR) and immunohistochemistry validation. PCNA is similar to the P53 gene and has been widely implicated in various cancers including gliomas. Therefore, the expression status of PCNA in our study was considered as a reference to test our whole experimental scheme, and the results indicate that our methodology is valid. Although a few studies have reported the overexpression of the CDC2, CDK2 and CCNB2 genes in glioma cell lines, we are the first to identify the statuses of these genes in human astrocytoma tissues at the mRNA and protein levels. The results of the gene validations strongly suggested that the genes play an important role in astrocytomas and could potentially be valuable in the diagnosis and treatment of astrocytoma.

Cancer cells display widespread genetic and epigenetic abnormalities, but the contribution to disease risk, particularly in normal tissue before disease, is not yet established. Genome-wide hypomethylation occurs frequently in tumors and may facilitate chromosome instability, aberrant transcription and transposable elements reactivation. Several epidemiologic case-control studies have reported genomic hypomethylation in peripheral blood of cancer patients, suggesting a systemic effect of hypomethylation on disease predisposition, which may be exploited for biomarker development. However, more recent studies have failed to reproduce this. Here, we report a meta-analysis, indicating a consistent inverse association between genomic 5-methylcytosine levels and cancer risk [95% confidence interval (CI), 1.2-6.1], but no overall risk association for studies using surrogates for genomic methylation, including methylation at the LINE-1 repetitive element (95% CI, 0.8-1.7). However, studies have been highly heterogeneous in terms of experimental design, assay type, and analytical methods. We discuss the limitations of the current approaches, including the low interindividual variability of surrogate assays such as LINE1 and the importance of using prospective studies to investigate DNA methylation in disease risk. Insights into genomic location of hypomethylation, from recent whole genome, high-resolution methylome maps, will help address this interesting and clinically important question.

Several genome-wide association studies on breast cancer have reported similar findings of a new cancer susceptibility locus, 8q24 rsl3281615. Subsequent case-control studies have rapidly investigated the association between the single nucleotide polymorphism of rsl3281615 at chromosome 8q24 and breast cancer risk, but the effect of 8q24 rsl3281615 polymorphism on breast cancer is still unclear due to the inconsistence among those studies. Given the contradictory findings, a meta-analysis was performed to determine the association between 8q24 rsl3281615 polymorphism and breast cancer risk. 12 eligible case-control studies with a total of 42,508 cases and 53,928 controls were finally included into this meta-analysis by searching the PubMed, Embase, and China Biology Medicine (CBM) databases. We estimated the summary odds ratio (OR) with its corresponding 95 % confidence interval (95 % CI) to assess this association. Meta-analyses of total 12 studies showed 8q24 rsl3281615 polymorphism was significantly associated with an increased risk of breast cancer in all contrast models (OR(G vs. A) = 1.10, 95 % CI 1.05-1.14, P (OR) < 0.001; OR(GG vs. AA) = 1.20, 95 % CI 1.11-1.29, P (OR) < 0.001; OR(AG vs. AA) = 1.08, 95 % CI 1.05-1.12, P (OR) < 0.001; OR(GG vs. AA +AG) = 1.13, 95 % CI 1.07-1.19, P (OR) < 0.001; OR(GG+AG vs. AA) = 1.13, 95 % CI 1.07-1.19, P (OR) < 0.001). Meta-analyses of studies with high quality showed that 8q24 rsl3281615 polymorphism was still significantly associated with an increased risk of breast cancer under the five genetic contrast models. Sensitivity analyses by sequential omission of any individual studies and subgroup analyses by ethnicity further identified the significant association between 8q24 rsl3281615 polymorphism and breast cancer risk. Conclusively, this meta-analysis shows a significant association between 8q24 rsl3281615 polymorphism and breast cancer risk.

XRCC1 polymorphism is a research hotpot in individual treatment for non-small cell lung cancer (NSCLC). To obtain the association between XRCC1 polymorphism and clinical outcome of platinum-based treatment for NSCLC, a meta-analysis was conducted.

Published data on the association between three novel functional polymorphisms (rs11200014, rs2981579, and rs2981578) in the promoter of FGFR2 gene and breast cancer risk are inconclusive. The aim of this human genome epidemiology review and meta-analysis was to derive a more precise estimation of the relationship. A literature search of Pubmed, Embase, Web of science, and CBM databases from inception through July 2012 was conducted. Seventeen studies were included with a total of 21,742 breast cancer cases and 31,125 healthy controls. Crude odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of association in allele model, dominant model, recessive model, homozygous model, and heterozygous model. When all the eligible studies were pooled into the meta-analysis, remarkable associations between the rs11200014 (A>G) polymorphism and breast cancer risk were detected in Caucasians (G vs. A: OR = 1.28, 95 % CI: 1.21-1.35; GG/AG vs. AA: OR = 1.32, 95 % CI: 1.18-1.48), but not in Asians and Africans. In addition, there were statistically significant associations between the rs2981579 (G>A) polymorphism and increased risk of breast cancer risk in all ethnicities (A vs. G: OR = 1.20, 95 % CI: 1.11-1.29; AA/GA vs. GG: OR = 1.32, 95 % CI: 1.18-1.48; AA vs. GG: OR = 1.67, 95 % CI: 1.55-1.81), including Caucasians, Asians, and Africans. However, the TT genotype of rs2981578 (C>T) polymorphism might decrease breast cancer risk (TT vs.

Recent genome-wide association study has identified a genetic variant rs4973768, located in 3'-UTR of solute carrier family 4, sodium bicarbonate cotransporter, member 7 (SLC4A7), was associated with increased risk of breast cancer (BC). However, several following replication studies cannot yield consistent results. We thus conducted a hospital-based case-control study including 485 patients and 514 controls, combined a meta-analysis including 108,632 cases and 135,818 controls to explore the relationship between this variant and BC risk. Our case-control study showed that rs4973768 was significantly associated with increased BC risk with the odds ratio (OR) of 1.29 (95 % confidence interval [CI]: 1.04-1.60) under the allelic model. In addition, the meta-analysis also indicated that the variant slightly increased the risk of BC with the pooled OR of the per-allele effect being 1.08 (95 % CI: 1.04-1.11) although with significant heterogeneity between studies. Stratified analyses showed that ethnicity, sample size, and study design may explain part of the heterogeneity. Moreover, the bioinformatics analysis suggested that this variant may influence the transcriptional capacity of SLC4A7. In summary, our results showed that the SLC4A7 variant, rs4973768, is associated with risk of BC although the underlying biologic mechanism warrants further studies.

Results from published studies on the association between the catechol-O-methyltransferase (COMT) Val158Met polymorphism and prostate cancer (PCa) risk are inconsistent. To derive a more precise estimate, we performed a meta-analysis.

Cyclin D1 (CCND1) plays a critical role in the G1 to S-phase cell cycle transition. Data on the association between the CCND1 A870G polymorphism and oral cancer are conflicting. To assess the relationship between the CCND1 A870G genotype and the risk of developing oral cancer, we performed a meta-analysis. We searched PubMed to December 1, 2011, for studies on this topic that had been published in the English. For each study, we calculated odds ratios (ORs) and 95 % confidence intervals (CIs), assuming the frequency of allele comparison, homozygote comparison, recessive and dominant genetic models. We then calculated pooled ORs and 95 % CIs. Seven studies were included in the meta-analysis. The CCND1 G allele was not associated with oral cancer in the frequency of allele comparison (G vs. A: OR = 0.882; 95 % CI = 0.684-1.137; p = 0.001 for heterogeneity). In the subgroup analysis, the CCND1 G allele was associated with a borderline significantly decreased risk of developing oral cancer in Asians in the frequency of allele comparison (G vs. A: OR = 0.800; 95 % CI = 0.636-1.006; p = 0.089 for heterogeneity), and the association between the GG genotype and oral cancer was significant in Asians with respect to both the homozygote comparison (GG vs. AA: OR = 0.644; 95 % CI = 0.491-0.843; p = 0.186 for heterogeneity) and the dominant genetic model (GG + AG vs. AA: OR = 0.713; 95 % CI = 0.584-0.870; p = 0.293 for heterogeneity). Our analysis provides evidence that genotypes for the CCND1 A870G polymorphism may be associated with an increased risk of developing oral cancer in the Asian population.

The association between NAD(P)H:quinone oxidoreductase 1 (NQO1) gene C609T polymorphism (rs1800566) and lung cancer has been widely evaluated, and a definitive answer so far is lacking. We first conducted a case-control study to assess this association in northeastern Han Chinese, and then performed a meta-analysis to further address this issue.

Inconsistency of the association of polymorphisms of XRCC7 with cancer is noted. Three commonly studied XRCC7 polymorphisms including rs7003908 (T>G), rs7830743 (A>G), and rs10109984 (T>C) were selected to explore their association with risk of development of cancer by meta-analysis of published case-control studies. The results showed that no significant associations with cancer risk were found in any model in terms of rs7003908, rs7830743 and rs10109984 when all studies were pooled into the meta-analysis. But when stratified by cancer type, statistically significantly elevated cancer risk was only found in prostate cancer for rs7003908 (GG vs. TT: OR = 1.845, 95 % CI = 1.178-2.888; dominant model: OR = 1.423, 95 % CI = 1.050-1.929; recessive model: OR = 1.677, 95 % CI = 1.133-2.482). In the subgroup analysis by ethnicity or study design, no significantly increased risks were found for all three polymorphisms. This meta-analysis suggests that XRCC7 rs7003908 polymorphism may contribute to cancer susceptibility for prostate cancer, which is recommended to be included in future large-sample studies and functional assays.

The x-ray cross complementing group 1 gene (XRCC1) is crucial to proper repair of DNA damage such as single-strand DNA breaks. A non-synonymous polymorphism in XRCC1, 399 G → A, has been shown to reduce effectiveness of such DNA repair and has been associated with the risk of certain cancers. The known risk for glioma from high dose ionizing radiation makes associations between this polymorphism and glioma of particular interest.

The main objective of this study was to perform a systematic review and meta-analysis on the risk of developing malignant paraganglioma (PGL) in SDHB-mutation and SDHD-mutation carriers. PubMed, EMBASE, Web of Science, COCHRANE and Academic Search Premier (2000-August 2011) and references of key articles were searched to identify potentially relevant studies. The main outcomes were the pooled incidence and prevalence of malignant PGL in SDHB-mutation and SDHD-mutation carriers. A meta-analysis was performed with an exact likelihood approach using a logistic regression with a random effect at the study level. Twelve studies were included. The pooled incidence of malignant PGL in populations comprising both asymptomatic mutation carriers and mutation carriers with manifest non-malignant PGL was 17% (95% CI 10 to 28) for SDHB-mutation carriers and 8% (95% CI 2 to 26) for SDHD-mutation carriers. The pooled risk in prevalence studies was 13% (95% CI 4 to 34) and 4% (95% CI 2 to 7), respectively. In studies comprising only mutation carriers with manifest disease, the pooled prevalence was 23% (95% CI 16 to 33) for SDHB-mutation and 3% (95% CI 1 to 10) for SDHD-mutation carriers. Incidence and prevalence of malignant PGL are higher in SDHB-mutation than in SDHD-mutation carriers, but lower in SDHB-mutation carriers than hitherto appreciated.

We synthesised the evidence of microRNAs as prognostic biomarkers in lung cancer. Studies were identified by searching PubMed, Embase and Web of Science until March 2012. Descriptive characteristics for studies were described and an additional meta-analysis for two specific microRNAs (miR-21 and miR-155) which were studied extensively was performed. Pooled hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated. The median study size was 88 patients (interquartile range [IQR]=53-193) and the median HR in the studies that reported statistically significant results was 2.855 (IQR=2.01-5.035). For the studies evaluating miR-21's association with clinical outcomes, the pooled HR suggested that high expression of miR-21 has a negative impact on overall survival (OS) in non-small cell lung cancer (NSCLC) (HR=2.32[1.17-4.62], P<0.05) and recurrence-free survival (RFS)/cancer-specific survival (CSS) in lung adenocarcinoma (HR=2.43[1.67-3.54], P<0.001). As for miR-155, the pooled HR for OS was 2.09 (95%CI: 0.68-6.41, P>0.05) which was not statistically significant, but for RFS/CSS was 1.42 (95% CI: 1.10-1.83, P=0.007). These results indicate that microRNAs show promising associations with prognosis in lung cancer; moreover, specific microRNAs such as miR-21 and miR-155 can predict recurrence and poor survival in NSCLC.

Epidemiological studies of the association of variants p53 Arg72Pro and MDM2 single-nucleotide polymorphism 309 (SNP309) with glioma risk have produced inconsistent results. The aim of the current study was to evaluate the association of these 2 variants with glioma susceptibility using a meta-analysis approach. For p53 Arg72Pro, 10 case-control studies including 2587 glioma patients and 4061 unrelated controls were identified. The pooled odds ratios (ORs) for Arg/Pro heterozygotes and Pro/Pro homozygotes were 1.08 [95% confidence interval (95%CI) = 0.85-1.37] and 1.08 (95%CI = 0.85-1.36), respectively, when compared to Arg/Arg carriers. Under the dominant effect model, Pro allele carriers also showed no significantly elevated glioma risk (pooled OR = 1.11, 95%CI = 0.90-1.38), and similar results were found under the recessive-effect model (pooled OR = 1.17, 95%CI = 0.85-1.61). For variant MDM2 SNP309, 3 case-control studies including 606 cases and 309 controls were identified. A marginal association with glioma risk was found for heterozygous G/T carriers (pooled OR = 1.95, 95%CI = 1.00- 3.81), whereas homozygous G/G carriers showed an increased but not significantly elevated risk of glioma (pooled OR = 2.14, 95%CI = 0.71-6.45) compared with that of T/T homozygotes. We also found no significant association between the MDM2 SNP309 polymorphism and glioma risk (pooled OR = 1.86, 95%CI = 0.94-3.67 and pooled OR = 1.25, 95%CI = 0.62-2.56, respectively) under the dominant and recessive models. Taken together, the current data suggested that the 2 polymorphisms may not contribute to glioma susceptibility.

The association between COMT Val158Met polymorphism and prostate cancer has been evaluated. However, the results of these studies on the association remain conflicting. To derive a more precise estimation of the relationship, a meta-analysis was performed. A comprehensive search was conducted to identify the eligible studies of COMT Val158Met polymorphism and prostate cancer risk. Summary odds ratios (OR) and 95 % confidence interval (CI) for COMT Val158Met polymorphism and prostate cancer were calculated. Statistical analysis was performed with the software program Review Manage (Version 5.0) and Stata (Version 12.0). Six case-control studies, totally 4,118 persons including 2,143 cases and 1,975 controls, met the included criteria and thus were selected. Our analysis suggested that Val158Met polymorphism was associated with prostate cancer risk in overall population. Collectively, the results of the present study suggest that significant associations of COMT Val158Met polymorphisms with prostate cancer were observed (for additive model: OR = 1.068, 95 % CI = 1.002-1.138, P (heterogeneity) = 0.363, P = 0.043; for dominant model: OR = 1.266, 95 % CI = 1.057-1.517, P (heterogeneity) = 0.000, P = 0.011; for recessive model: OR = 1.050, 95 % CI = 0.961-1.146, P (heterogeneity) = 0.558, P = 0.279; and Val allele versus Met allele OR = 0.932, 95 % CI = 0.894-0.971, P (heterogeneity) = 0.272, P = 0.001). In the subgroup analysis, we detected no significant association between the COMT 158 Val/Met genotype and prostate cancer risk in Caucasian and Asian populations, while the contrary result for additive model (OR = 2.43, 95 % CI = 1.08-5.43, P (heterogeneity) = 0.04, P = 0.03) in Asian populations. The result of this meta-analysis suggests that COMT l58Val/Met polymorphism might be contributed to the overall prostate cancer risk.

Previous studies show that X-ray cross-complementing group 1 (XRCC 1) Arg399Gln may result in variations in repair efficiency of DNA damage, and this repair deficit may eventually cause individual susceptibility to glioma. However, published data regarding the association between XRCC 1 Arg399Gln polymorphism and glioma risk was contradictory. The aim of this study was to derive a more precise estimation of the association of XRCC 1 Arg399Gln polymorphism with glioma risk by performing a meta-analysis of eligible studies. Odds ratios (ORs) and 95 % confidence intervals (95 %CIs) were used to assess the strength of the association. We performed a meta-analysis of eleven published studies that included 2,808 glioma cases and 3,114 controls. Overall, there was a significant association between XRCC1 Arg399Gln polymorphism and glioma risk in two genetic models (for ArgGln vs ArgArg: OR = 1.30, 95 % CI 1.01-1.68; for GlnGln/ArgGln vs ArgArg: OR = 1.28, 95 % CI 1.01-1.62). In the stratified analysis by ethnicity, the XRCC1 Arg399Gln polymorphism had a higher risk of glioma development among Asians (for Gln vs Arg: OR = 1.34, 95 % CI 1.12-1.61; for GlnGln vs ArgArg: OR = 1.72, 95 % CI 1.18-2.51; for ArgGln vs ArgArg: OR = 1.31, 95 % CI 1.01-1.71; for GlnGln/ArgGln vs ArgArg: OR = 1.41, 95 % CI 1.10-1.80; for GlnGln vs ArgArg/ArgGln: OR = 1.48, 95 % CI 1.05-2.09)., but not among Caucasians. In conclusion, the results suggest that the XRCC 1 Arg399Gln polymorphism may contribute to the susceptibility of glioma in Asians.

A debate exists about whether interleukin 10 (IL-10) polymorphisms (IL-10-1082G/A and IL-10-592C/A) confer additional risk for cervical cancer. To derive a more precise estimation of the relationship between IL-10 polymorphisms and cervical cancer risk, we conducted a meta-analysis of all available studies relating the -1082G/A and -592C/A polymorphisms of the IL-10 gene to the risk of developing cervical cancer.