Many studies have been carried out to test the hypothesis that the NQO1 C609T polymorphism might be associated with the risk of esophageal cancer. However, the results are poorly consistent, partly due to genetic or other sources of heterogeneity. To investigate the association between this polymorphism and the risk of esophageal cancer, a meta-analysis was performed.

Glioma is a highly invasive, rapidly spreading form of brain cancer, while its etiology is largely unknown. A few recently reported studies have been developed using gene expression microarrays of glioma to identify differentially expressed genes from several to hundreds. This study was designed to analyze vast amounts of glioma-related microarray data and screen the key genes and pathways related to the development and progression of glioma. We used gene set enrichment analysis (GSEA) and meta-analysis of seven included studies after standardized microarray preprocessing, which increased concordance between these gene datasets. After GSEA, there were 14 mixing pathways including 13 up- and 1 down-regulated pathways. Based on the meta-analysis, 268 significant genes were screened out (P < 0.05); there were 249 genes identified by Kyoto Encyclopedia of Genes and Genomes (KEGG), and 27 KEGG pathways closely related to the set of the imported genes were identified. At last, six consistent pathways and key genes in these pathways related to glioma were obtained with combined GSEA and meta-analysis. The gene pathways that we identified could provide insight concerning the development of glioma. Further studies are needed to determine the biological function for the positive genes.

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate. The single nucleotide polymorphism (SNP), C677T (Ala>Val, rs1801133), has been confirmed to decrease the enzyme activity. The association between C677T and cervical cancer susceptibility has been widely studied. However, the results were inconsistent. In order to elucidate the role of this SNP in cervical cancer, a meta-analysis was conducted.

Published data on the association between interleukin-10 (IL-10) gene polymorphisms and diffuse large B-cell lymphoma (DLBCL) risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed, focusing on four major IL-10 gene variants in the promoter region: -3575T/A, -1082A/G, -819C/T and -592C/A. We applied the false discovery rate (FDR) method to adjust for multiple testing. A significant association between IL-10 -3575T/A polymorphism and the risk of DLBCL was observed in the pooled 10 case-control studies (A vs. T: OR=1.16, 95% CI=1.08-1.25, P<0.0001; AA+TA vs. TT: OR=1.20, 95% CI=1.08-1.33, P=0.0009; AA vs. TA+TT: OR=1.25, 95% CI=1.09-1.44, P=0.001). The results indicated that carriers of -1082G allele (-1082GG/GA genotypes) had a nearly 30% increased risk of DLBCL, as compared with carriers of -1082AA genotype (GG+GA vs. AA: OR=1.30, 95% CI=1.08-1.57, P=0.005). When P-values were not adjusted for multiple testing, the risk was significantly decreased among people with -592AA genotype (AA vs. AC+CC: OR=0.63, 95% CI=0.43-0.94, P=0.02), while carriers with -819TT genotype also modestly weakened the DLBCL susceptibility at a marginal level of significance (TT vs. CT+CC: OR=0.59, 95% CI=0.35-0.99, P=0.05). However, these associations were not significant after correction for multiple testing. This meta-analysis suggests that IL-10 -3575A allele confers a greater risk to DLBCL susceptibility, while -1082A/G polymorphism also has significant association with DLBCL risk. These results may help to further clarify the malignancy-risk gene signature of DLBCL, and thus have prognostic and predictive value especially for early-stage DLBCL.

We carried out a meta-analysis focusing on the relationship between length of AIB1 gene poly-Q repeat domain as a modifier of breast cancer (BC) susceptibility in patients with BRCA1 and BRCA2 mutation carriers.

Previous reports implicate XRCC1 Arg399Gln polymorphism as a possible risk factor for several cancers. Published meta-analyses have been conducted on the association of XRCC1 Arg399Gln polymorphism with susceptibility to bladder cancer, and have generated conflicting results. The present study aimed to derive a more precise estimation of the relationship. Updated meta-analyses assessing the association of XRCC1 Arg399Gln polymorphism with bladder cancer were conducted and subgroup analyses on ethnicity, smoking status and source of controls were further performed. Eligible studies were identified for the period up to May 2012. A total of 19 case-control studies comprising 5767 cases and 6919 controls were lastly selected for analysis. The overall data failed to indicate significant associations between XRCC1 Arg399Gln polymorphism and bladder cancer risk (Gln/Gln versus Arg/Arg: odds ratio (OR) = 0.97; 95% CI = 0.85-1.10; dominant model: OR = 1.02; 95% CI = 0.94-1.09; recessive model: OR = 0.95; 95% CI = 0.84-1.07). In subgroup analyses stratified by ethnicity, smoking status and source of controls, respectively, similar results were obtained. In conclusion, the results of the present study suggest that XRCC1 Arg399Gln polymorphism might not modify the susceptibility to bladder cancer. Further large and well-designed studies are needed to confirm this conclusion.

Genetic variation in the CASP-8 gene reportedly can increase cancer susceptibility by regulating tumor cell proliferation and apoptosis. Several studies have investigated this possibility; however, the conclusions remain controversial. We made a Human Genome Epidemiology (HuGE) review and did a meta-analysis to explore the association between CASP-8 gene polymorphisms and cancer risk in Asian populations. Based on the inclusion criteria, 12 case-control studies comprising 7720 cancer cases and 9404 healthy controls were retrieved. Meta-analysis results showed that the rs3834129*del allele/carrier were associated with decreased risk of cancer in Asian populations [del allele: odd ratio (OR) = 0.79, 95% confidence interval (95%CI) = 0.75-0.83, P < 0.001; del carrier: OR = 0.77, 95%CI = 0.72-0.82, P < 0.001]. Subgroup analysis showed that the rs3834129*del allele/carrier are protective factors for cancer risk in Chinese populations (del allele: OR = 0.77, 95%CI = 0.73-0.81, P < 0.001; del carrier: OR = 0.75, 95%CI = 0.70-0.80, P < 0.001), but not in Indian and Korean populations. Furthermore, the rs6704688*T allele/carrier, rs3769827*C allele/carrier, rs3769825*C allele/carrier were associated with decreased risk of cancer in Asian populations (all P < 0.05). While the rs7608692*A allele was associated with increased risk of cancer risk in Asian populations (OR = 1.35, 95%CI = 1.02-1.78, P = 0.03). There was also no significant association between rs3769818, rs13030042, rs13030042, rs1045494, rs1045494, rs2823, or rs113686495, and cancer risk in Asian populations (all P > 0.05). This meta-analysis suggests that the rs3834129*del allele/ carrier, rs6704688*T allele/carrier, rs3769827*C allele/carrier, and rs3769825*C allele/carrier might be protective factors for cancer risk in Asian populations, while the rs7608692*A allele might be a risk factor for cancer risk in Asian populations.

Cytochrome P450 1A1 (CYP1A1), an important phase I xenobiotic metabolizing enzyme, is responsible for metabolizing numerous carcinogens, particularly polycyclic aromatic hydrocarbons. The genetic polymorphism of CYP1A1 at the site of MspI (CYP1A1 MspI) has been implicated in prostate cancer risk, but the results of individual studies remain conflicting and inconclusive. The aim of this meta-analysis was to investigate the association of CYP1A1 MspI polymorphism with prostate cancer risk more precisely. We performed a comprehensive search of the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases from their inception up to September 20, 2012 for relevant publications. The pooled odds ratios with the corresponding 95% confidence intervals (95% CIs) were calculated to assess the association of CYP1A1 MspI polymorphism with prostate cancer risk. In addition, stratified analyses by ethnicity and sensitivity analyses were conducted for further estimation. Sixteen eligible publications with 6,411 subjects were finally included into the meta-analysis after checking the retrieved papers. Overall, meta-analysis of total studies suggested that individuals carrying the TC genotype and a combined C genotype (CC + TC) were more susceptible to prostate cancer (OR(TC vs. TT) = 1.33, 95% CI 1.10-1.61, P(OR) = 0.004; OR(CC+TC vs. TT) = 1.27, 95% CI 1.05-1.55, P(OR) = 0.016). Stratified analysis of high quality studies also confirmed the significant association (OR(TC vs. TT) = 1.32, 95% CI 1.04-1.67, P(OR) = 0.024; OR(CC+TC vs. TT) = 1.30, 95% CI 1.02-1.66, P(OR) = 0.035). In subgroup analyses by ethnicity, a significant association between the CYP1A1 MspI polymorphism and risk of prostate cancer was found among Asians (OR(TC vs. TT) = 1.44, 95% CI 1.20-1.72, P(OR) < 0.001; OR(CC+TC vs. TT) = 1.33, 95% CI 1.12-1.58, P(OR) = 0.001), but not in Caucasians or mixed populations. The meta-analysis suggests an important role of the CYP1A1 MspI polymorphism in the risk of developing prostate cancer, especially in Asians.

The current management of locally advanced rectal cancer involves total mesorectal excision, which may be preceded by neo-adjuvant chemoradiotherapy (CRT). Individual patient response to CRT is variable and reproducible biomarkers of response are needed. The role of the V-Ki-ras2 Kirsten rat sarcoma viral oncogene (KRAS) in rectal cancer remains equivocal. The aim of the current study was to systematically appraise the effect of KRAS mutation on outcomes following CRT for rectal cancer.

Accumulating evidence has suggested that Mothers against decapentaplegic homolog 7 (SMAD7) rs12953717 polymorphism might be related to cancer risk. However, epidemiologic findings have been inconsistent. We therefore performed a meta-analysis to clarify the association between the SMAD7 rs12953717 polymorphism and cancer risk.

Objective The glutathione S-transferase P1 (GSTP1) gene has been suggested to play an important role in the pathogenesis of oral cancer. However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association of GSTP1 Ile105Val polymorphisms with oral cancer risk. Methods Published literature from PubMed and EMBASE were retrieved. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. Results 13 studies (1803 oral cancer cases and 2998 controls) for GSTP1 Ile105Val polymorphism were included in the meta-analysis. The results indicated that there was no significant association between GSTP1 Ile105Val polymorphism and oral cancer in the overall population (OR=1.30, 95%CI=0.92-1.38, I(2)=48.0%, p for heterogeneity=0.027). Further subgroup analysis by ethnicity suggested that GSTP1 Ile105Val polymorphism was significantly associated with oral cancer only in East Asians (OR=1.64, 95%CI=1.16-2.31, I(2)=0.0%, p for heterogeneity=0.525), but not in Caucasians (OR=1.16, 95%CI=0.73-1.82, I(2)=7.5%, p for heterogeneity=0.299), Africans (OR=1.10, 95%CI=0.37-3.28), South Asians (OR=1.20, 95%CI=0.69-2.08, I(2)=74.3%, p for heterogeneity=0.021) and mixed population (OR=0.91, 95%CI=0.70-1.20, I(2)=39.7%, p for heterogeneity=0.174). Conclusions The present meta-analysis has limited evidence to support the association of GSTP1 Ile105Val polymorphism with HCC risk in the overall population. However, GSTP1 Ile105Val polymorphism might be associated with risk of oral cancer in East Asians.

Central nervous system (CNS) disease as the site of first relapse after exposure to adjuvant trastuzumab has been reported. We carried out comprehensive meta-analysis to determine the risk of CNS metastases as the first site of recurrence in patients with HER2-positive breast cancer who received adjuvant trastuzumab.

Many studies have studied the associations between 5, 10-methylene tetrahydrofolate reductase (MTHFR) polymorphisms and susceptibilities of cervical cancer and cervical intraepithelial neoplasia (CIN); however, the results were inconsistent. The aim of this study was to further assess the relationships by the method of meta-analysis.

There are several well-established environmental risk factors for ovarian cancer, and recent genome-wide association studies have also identified six variants that influence disease risk. However, the interplay between such risk factors and susceptibility loci has not been studied.

Angiogenesis and lymphangiogenesis are important in the progression of melanoma. We investigated associations between genetic variants in these pathways with sentinel lymph node (SLN) metastasis and mortality in 2 independent series of patients with melanoma.

Aristolochic acid is a toxin found in plants of the genus Aristolochia, to which humans can be exposed either through certain Chinese herbal medicines or through inadvertent commingling with food crops. Our objective was to estimate cumulative exposures of aristolochic acid associated with increased risk of end-stage renal disease (ESRD), and to conduct a systematic review and meta-analysis on aristolochic acid-induced upper tract urothelial carcinoma (UUC).

CYP1A1 plays an essential role in pathogenesis of head and neck cancers. Functional CYP1A1 Ile462Val and MspI single nucleotide polymorphisms (SNP) are considered to have significant effects on risk of head and neck cancers. Several case-control studies have examined how these genetic polymorphisms are involved in development of this group of malignancies, but the conclusions are inconsistent. Therefore, we conducted this meta-analysis to systematically examine the associations between these functional genetic variants and head and neck cancer risk. A total of 28 studies are eligible for CYP1A1 Ile462Val SNP (4639 patients and 4701 controls), and 22 studies for MspI SNP (4168 patients and 4638 controls). Pooled odds ratios (ORs) and the 95% confidence interval (95% CI) were appropriately calculated using either fixed-effect model or random-effect model. There was no association between Ile462Val polymorphism and head and neck cancer risk (OR = 1.23, 95% CI = 0.99-1.53, P = 0.062). However, in a stratified analysis, a statistically significant correlation between this SNP and pharyngeal cancer risk was observed (OR = 1.76, 95% CI = 1.32-2.33, P < 0.001). For MspI SNP, our data indicated that carriers of TC and CC genotypes had a 34% increased risk to develop head and neck cancers compared to TT carriers (95% CI = 1.15-1.57, P < 0.001). This effect was even more pronounced in smokers (OR = 2.98, 95% CI = 1.69-5.26, P < 0.001), demonstrating that gene-smoking interaction intensifying carcinogenesis may exist. These findings reveal that the functional CYP1A1 MspI genetic variant, alone and in combination with smoking, plays a more important role in pathogenesis of head and neck cancers.

The MNS16A polymorphism in the telomerase reverse transcriptase (TERT) gene has been implicated in cancer risk in multiple populations and various types of cancers; however, the results of previous studies exploring this association were inconclusive. To more precisely evaluate the relationship between the TERT MNS16A polymorphism and cancer risk, we performed a meta-analysis based on 8 studies described in 7 articles comprising 7864 controls and 4355 cases. The summary odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were estimated to assess the strength of the association in a fixed-effects model or a random-effects model where appropriate. Heterogeneity among articles and their publication bias were also tested. Overall, the pooled results indicated that the MNS16A polymorphism was significantly associated with increased cancer risk in the homozygote comparison model (SS vs. LL: OR=1.280, 95% CI 1.060-1.547) and the recessive model (SS vs. LL+SL: OR=1.201, 95% CI 1.004-1.436). In the stratified analyses, a statistically significant association was observed among Caucasians and in population-based studies. We also performed the analyses by cancer type, and a significantly increased risk of glioma was found in four genetic models. Our results suggest that the TERT MNS16A polymorphism most likely contributes to an increased risk of cancer. Moreover, the same relationship was found when the studies were stratified by cancer type, ethnicity and source of controls.

Genome-wide association studies (GWASs) have identified multiple common genetic variants associated with an increased risk of testicular germ cell tumors (TGCTs). A previous GWAS reported a possible TGCT susceptibility locus on chromosome 1q23 in the UCK2 gene, but failed to reach genome-wide significance following replication. We interrogated this region by conducting a meta-analysis of two independent GWASs including a total of 940 TGCT cases and 1559 controls for 122 single-nucleotide polymorphisms (SNPs) on chromosome 1q23 and followed up the most significant SNPs in an additional 2202 TGCT cases and 2386 controls from four case-control studies. We observed genome-wide significant associations for several UCK2 markers, the most significant of which was for rs3790665 (PCombined = 6.0 × 10(-9)). Additional support is provided from an independent familial study of TGCT where a significant over-transmission for rs3790665 with TGCT risk was observed (PFBAT = 2.3 × 10(-3)). Here, we provide substantial evidence for the association between UCK2 genetic variation and TGCT risk.

Interleukin-10 (IL-10) is a multifunctional cytokine which participates in the development and progression of various malignant tumors. To date, a number of case-control studies were conducted to detect the association between IL-10-592C>A polymorphism and cancer risk in humans. However, the results of these studies on the association remain conflicting. In an effort to solve this controversy, we performed a meta-analysis based on 70 case-control studies from 65 articles, including 16 785 cancer cases and 19 713 controls. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. The overall results suggested that the variant homozygote genotype AA of the IL-10-592C>A polymorphism was associated with a moderately decreased risk of all cancer types (OR = 0.90, 95% CI = 0.83-0.98 for homozygote comparison, OR = 0.92, 95% CI = 0.86-0.98 for recessive model). In the stratified analyses, the risk remained for studies of smoking-related cancer, Asian populations and hospital-based studies. These results suggested that the IL-10-592C>A polymorphism might contribute to the cancer susceptibility, especially in smoking-related cancer, Asians and hospital-based studies. Further studies are needed to confirm the relationship.