The aim of our meta-analysis was to assess the association between NFKB1 -94ins/delATTG promoter polymorphism and cancer risk. Eleven studies that included data from 2,743 cases and 2,195 controls were identified. When all groups were pooled, we did not detect the association between NFKB1 -94ins/delATTG promoter polymorphism and cancer risk. In the subgroup analysis, we detected the association of NFKB1 -94ins/delATTG promoter polymorphism with cancer in Caucasian population. The association also was found in Asian population. This meta-analysis demonstrates the association of NFKB1 -94ins/delATTG promoter polymorphism with cancer in Caucasian and Asian populations, and this association is ethno-specific.

Although extensive literature exists on cancer biomarkers few have found entry into clinical use. In particular, the cancer metastasis gene Osteopontin has been investigated extensively but it has not yet been applied to routine diagnostics. Here, we conduct a meta-analysis of data from the published literature and from RNA microarrays deposited in Oncomine. Osteopontin has been associated with 34 cancers. It is a marker for breast, cervical, colorectal, head and neck, liver, lung, ovarian and prostate cancers, as well as for sarcoma. Osteopontin is overexpressed in the metastases of colorectal cancers, lung cancers and melanomas, but not in ovarian cancer. Further, Osteopontin is indicative of the underlying mechanism of transformation only in certain virally induced tumors, where its function as a TH1 cytokine likely plays important roles. These results refine the value of Osteopontin as a cancer biomarker.

The association between vascular endothelial growth factor (VEGF) +936 C/T gene polymorphisms and gastric cancer risk is still controversial and ambiguous. The objective of our study was to investigate this association. The Medline and Embase databases were searched by two investigators. Crude odds ratios (OR) and 95% confidence intervals (CI) were used to test the association between VEGF +936 C/T polymorphisms and gastric cancer risk. Our meta-analysis comprised seven case-control studies, which included 1,893 gastric cancer cases and 2,245 controls. The combined results showed that there was no relationship between VEGF +936 C/T gene polymorphisms and gastric cancer risk (CC: OR 0.97, 95% CI 0.85, 1.11; CT: OR 1.01, 95% CI 0.88, 1.16; TT: OR 1.10, 95% CI 0.79, 1.55). Subgroup analysis by ethnicity and stage, location, and Lauren classification of gastric cancer did not change the results. This meta-analysis suggests that there is no association between VEGF +936 C/T polymorphisms and gastric cancer risk. Further studies should pay attention to other potentially functional SNPs.

Cyclin D1 represents a key molecule in the regulation of cell cycle. CCND1 G870A (rs603965) polymorphism has drawn considerable attention as the A allele may generate a variant splice product with possible oncogenic actions. A meta-analysis examining the association between CCND1 G870A polymorphism and breast cancer risk was performed. Separate analyses on Caucasian and Chinese populations were also implemented. Eligible articles were identified for the period up to July 2010. Pooled odds ratios (OR) were appropriately derived from fixed-effects or random-effects models. Sensitivity analysis excluding studies whose genotype frequencies in controls significantly deviated from Hardy-Weinberg Equilibrium (HWE) was performed. Nine case-control studies on Caucasians (7,304 cases and 8,149 controls) and four case-control studies on Chinese (2,607 cases and 3,022 controls) were eligible. At the overall analysis the A allele seemed to be associated with elevated breast cancer risk; the effect seemed to be confined to homozygous carriers (pooled OR = 1.091, 95% CI: 1.008-1.179, P = 0.030, fixed effects) as heterozygous carriers did not exhibit significantly elevated breast cancer risk. No statistically significant associations were demonstrated in Caucasians. On the other hand, Chinese AA carriers exhibited marginally elevated breast cancer risk (pooled OR = 1.144, 95% CI: 0.984-1.329, P = 0.080, fixed effects). Nevertheless, the controls in two out of the four Chinese studies deviated from HWE. In conclusion, this meta-analysis suggests that the A allele of the CCND1 G870A polymorphism may confer additional breast cancer risk when it comes to homozygosity and Chinese populations. The need for additional, methodologically sound studies on Chinese populations seems warranted.

The matrix metalloproteinases (MMP) can degrade various components of the extracellular matrix and its functional genetic polymorphisms may be associated with breast cancer risk. However, this relationship remains controversial. A meta-analysis was conducted in order to investigate the potential association between four polymorphisms in the MMP gene and breast cancer risk. A database search yielded a total of 9 studies involving 2,597 cases and 2,618 controls. Four polymorphisms were included in the meta-analysis: MMP-1 -1607 2G/1G (rs1799750), MMP-2 -1306 C/T (rs243865), MMP-3 -1171 6A/5A (rs3025058) and MMP-9 -1562 C/T (rs3918242). Crude odds ratios (OR) with 95% confidence intervals (CI) were used to assess the strength of association. When all the studies were pooled into the meta-analysis, we found that breast cancer cases had a significantly higher frequency of CC genotype (OR = 1.27, 95% CI = 1.10, 1.47; P = 0.001) and lower frequency of CT genotype (OR = 0.78, 95% CI = 0.67, 0.91; P = 0.001) of MMP-2. No significant difference was found in any genotype of MMP-1, MMP-3 or MMP-9. In conclusion, this meta-analysis suggested that MMP-2 -1306 C/T polymorphism may contribute to breast cancer susceptibility. More studies were needed especially in Asians in the future.

To evaluate whether alcohol dehydrogenase-1B (ADH1B) His47Arg and aldehyde dehydrogenase-2 (ALDH2) Glu487Lys polymorphism is involved in the esophageal squamous cell carcinoma (ESCC) risk in Chinese Han population.

Inactivation of the tumor suppressor gene RASSF1A through methylation of the CpG islands within its promoter region as a prognostic factor for survival in non-small cell lung carcinoma (NSCLC) remains controversial. A meta-analysis of published studies investigating the effects of RASSF1A methylation on both relapse-free survival (RFS) and overall survival (OS) among NSCLC patients was performed. A total of 2802 patients from 19 eligible studies were included in the systematic review and 17 studies were included in the meta-analysis. In all, 32.6% of NSCLC patients had the methylated RASSF1A allele. Four of these studies investigated the correlation between RASSF1A methylation and RFS using univariate analysis. The univariate estimate for RFS was 1.87 [95% confidence interval (CI): 1.41-2.49; P < 0.0001] with no evidence of significant heterogeneity. Thirteen studies undertook univariate analyses of RASSF1A methylation and OS and 12 undertook multivariate analyses of RASSF1A methylation and OS. The pooled hazard ratio (HR) estimate for OS was 1.52 (95% CI: 1.33-1.74; P < 0.0001) by univariate analysis and 1.34 (95% CI: 1.15-1.57; P < 0.0001) by multivariate analysis. No significant heterogeneity was detected. For stages I-II NSCLC, the meta-risk remained highly significant by both univariate (HR = 1.94; 95% CI: 1.54-2.44; P < 0.0001) and multivariate analysis (HR = 1.39; 95% CI: 1.02-1.90; P = 0.039). This study shows that RASSF1A methylation appears to be an independent prognostic factor for poor survival in surgically treated NSCLC. However, the present findings require confirmation though adequately designed prospective studies.

A debate exists about whether glutathione S-transferase (GST) polymorphisms (GST mu-1 [GSTM1] null/present genotype and GST theta-1 [GSTT1] null/present genotype) confer additional risk for cervical cancer. This meta-analysis was aimed to examine the associations between the aforementioned polymorphisms and cervical cancer risk.

Colorectal cancer constitutes a significant proportion of the global burden of cancer morbidity and mortality. A number of studies have been conducted to explore whether TP53 codon 72 polymorphism is associated with colorectal cancer susceptibility. However, controversial results were obtained. In order to derive a more precise estimation of the relationship, we systematically searched Medline, Google scholar, and Ovid database for studies reported before May 2010. A total of 3603 colorectal cancer cases and 5524 controls were included. TP53 codon 72 polymorphism was not associated with colorectal cancer risk in all genetic models (for dominant model: OR = 0.99, 95% CI: 0.86-1.15; for recessive model: OR = 1.00, 95% CI: 0.81-1.23; for Arg/Pro vs. Arg/Arg: OR = 1.00, 95% CI: 0.87-1.15; for Pro/Pro vs. Arg/Arg: OR = 0.97, 95% CI: 0.76-1.25). In the subgroup analyses by ethnic groups and sources of controls, no significant associations were found in all models. Taken together, this meta-analysis suggested that the biologically usefulness of TP53 codon 72 polymorphism as a selection marker in colorectal cancer susceptibility may be very limited.

Many studies have examined the association between the APE1 T1349G (Asp148Glu) gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The PubMed, Embase, Web of Science, and CNKI database was searched for case-control studies published up to June 2010. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Ultimately, ten studies, comprising 2,696 lung cancer cases and 3,948 controls were included. Overall, for the G allele carriers (TG + GG) versus homozygote TT, the pooled OR was 1.037 (95% CI = 0.928-1.159 P = 0.001 for heterogeneity), for GG versus TT the pooled OR was 0.997 (95% CI = 0.861-1.154 P = 0.005 for heterogeneity). In the stratified analysis by ethnicity, significantly risks were not found among Asians or Caucasians. However, in the subgroup analyses by smoking status, significantly risks were found among smokers not in non-smokers. This meta-analysis suggested that the APE1 T1349G (Asp148Glu) polymorphism was not associated with lung cancer risk among Asians or Caucasians. But, the APE1 G allele was an increased risk factor for developing lung cancer among smokers.

Genome-wide association studies and subsequent replication studies have shown that single nucleotide polymorphisms (SNPs) in the chromosomal region 8q24 are associated with colorectal cancer susceptibility.

Polymorphisms in the melanocortin 1 receptor (MC1R) gene have been associated with increased risks of melanoma, but different approaches to study design, analysis, and reporting have hindered comparisons of findings. We aimed to harmonize the published data by conducting a systematic review and meta-analysis of MC1R variants and thereby estimate relative risks and population attributable fractions (PAFs). We identified 20 analytic studies reporting on 25 populations, which presented quantitative data on melanoma risks associated with any of nine MC1R variants. We separately pooled estimates of risk per person and risk per chromosome using a random effects model. Red hair color (RHC) variants had the highest risk of melanoma [summary odds ratios (OR) 2.44, 95% confidence interval (CI) 1.72-3.45, PAF 16.8% CI 0.119-0.202], but non-RHC variants were also associated with increased risk (summary OR 1.29, 95% CI 1.10-1.51, PAF 7.4% CI 0.030-0.112). The summary risk of melanoma associated with individual variants ranged from OR 2.40 for R142H to 1.18 for V60L, although significant heterogeneity was evident for most variants. PAFs ranged from 0.55% for I155T to 6.28% for R151C. Our findings suggest the nine most common MC1R variants make a sizeable contribution to the burden of melanoma. Melanoma research would be greatly assisted by standardized classifications for MC1R variants and consistent reporting conventions. More compatible and comparable research would allow for more powerful data that could be clinically applied to predict melanoma risk.

The expression profiles of microRNAs (miRNAs) are associated with the initiation and progression of human tumors. DNA microarrays are widely used to explore the expression patterns of miRNAs. Because of the limited sample size and experimental expense, the statistical power of individual research projects is not sufficient to yield a robust conclusion. However, collected microarray datasets of expression profiles provide opportunities to compile the information of individual studies. Our study carried out a comprehensive meta-analysis of miRNA expression microarray datasets from 28 published tumor studies; it comprises 33 comparisons and nearly 4,000 tumor and corresponding nontumorous samples. This work reports 52 miRNAs as common signatures that are dysregulated in tumors. In addition to the commonly altered miRNAs, five solid cancers displayed specific tissue patterns of altered miRNAs as well. The meta-analysis also revealed some novel tumor-related miRNAs such as hsa-miR-144, hsa-miR-130b, hsa-miR-132, hsa-miR-154, hsa-miR-192 and hsa-miR-345. We further validated the expression pattern of hsa-miR-154 in human hepatocellular carcinoma by RT-PCR. Restoration of intracellular miR-154 inhibited tumor cell malignance and the G(1)/S transition in cancer cells. Both bioinformatic prediction and western blotting demonstrated that miR-154 could target CCND2. In addition, expression patterns of miR-154 were inversely correlated with those of CCND2 in hepatocellular carcinoma. Overall, this study used a large-scale data analysis to identify a qualified list of miRNAs that are consistently changed in tumors, which could lead to a better understanding of human tumor etiology.

Interferon gamma (IFN-γ) plays a pivotal role in antiproliferative, antitumor and antiviral activities. The +874 polymorphism in IFN gene region reportedly affects cancer risk. However, pertinent studies offer conflicting results. To derive a more precise estimation, we performed a meta-analysis based on 1,929 cases and 2,830 controls from 17 published case-control studies, assessing the strength of the association using odds ratios with 95% confidence intervals. Our meta-analysis showed the evidence that IFN-γ +874 T/A was not associated with increased cancer risk in ethnicity and source of controls. However, stratified analysis by cancer type indicated a significantly increased risk of cervical cancer (AT vs. TT: OR = 1.10, 95% CI = 1.02-1.19, P = 0.961 for heterogeneity). Further prospective researches with a larger single study are required to evaluate any association with other types of cancer or in other populations.

Several polymorphisms of vascular endothelial growth factor (VEGF) such as 936 C/T, -2578 C/A, -406 C/T, and -1154 G/A polymorphism have been identified. Published data on the association between VEGF polymorphisms and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude OR with 95% CI was used to assess the strength of association between them. For VEGF 936C/T polymorphism, a total of 10 studies including 7,685 cases and 7,915 controls were involved in this meta-analysis. Overall, no significant associations were found between VEGF 936C/T polymorphism and breast cancer risk when all studies pooled into the meta-analysis (TC vs. CC: OR = 0.904, 95% CI = 0.797-1.024; TT vs. CC: OR = 0.974, 95% CI = 0.786-1.205; dominant model: OR = 0.911, 95% CI = 0.811-1.024; and recessive model: OR = 0.991, 95% CI = 0.801-1.226). In the subgroup analysis by ethnicity, still no significant associations were found for all comparison models. For -2578 C/A, -406 C/T, and -1154 G/A polymorphism, there were too limited data to perform a meta-analysis. In conclusion, this meta-analysis suggests that the VEGF 936C/T polymorphism may be not associated with 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.

Published data on the association between lymphocyte-specific protein 1 (LSP1) rs3817198T>C polymorphism and breast cancer risk are inconclusive. Hence, we conducted a meta-analysis of the LSP1 gene and risk of breast cancer to obtain the most reliable estimate of the association. PubMed, Embase and Web of Science databases were searched. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were extracted and pooled to assess the strength of the association between the LSP1 rs3817198T>C polymorphism and risk of breast cancer. A total of seven eligible studies including 33,920 cases and 35,671 controls based on the search criteria were involved in this meta-analysis. The distributions of genotypes in the controls were all in agreement with Hardy-Weinberg equilibrium. We observed that the LSP1 rs3817198T>C polymorphism was significantly correlated with breast cancer risk when all studies were pooled into the meta-analysis (the allele contrast model: OR = 1.06, 95% CI = 1.04-1.08; the homozygote codominant: OR = 1.14, 95% CI = 1.01-1.28). In the stratified analysis by ethnicity, significant association was observed in Caucasians for CC versus TT homozygote codominant model (OR = 1.25; 95% CI = 1.03-1.52) and for the recessive model (OR = 1.22; 95% CI = 1.02-1.47). There was significant association observed in Africans for CC versus TT homozygote codominant model (OR = 0.45; 95% CI = 0.22-0.92) and for the recessive model (OR = 0.43; 95% CI=0.22-0.88). Also, significant association was observed in mixed ethnicities for CC versus TT homozygote codominant model (OR = 1.12; 95% CI = 1.05-1.19). When stratified by study design, statistically significantly elevated risk was found in nested case-control studies (CC vs. TT: OR = 1.12, 95% CI = 1.05-1.19). But no significant association was observed for all comparison models between LSP1 rs3817198T>C polymorphism and breast cancer risk in hospital-based and people-based studies. When stratified by BRCA1 mutation carriers status, statistically significantly elevated risk was found in this meta-analysis (the allele contrast model: OR = 1.07, 95% CI = 1.01-1.14; the dominant model: OR = 1.09, 95% CI = 1.00-1.18). And significant association was found in the BRCA2 mutation carriers in the allele contrast (OR = 1.11, 95% CI = 1.03-1.20), the homozygote codominant (OR = 1.23, 95% CI = 1.04-1.47), the heterozygote codominant (OR = 1.12, 95% CI = 1.00-1.25) and the dominant models (OR = 1.14, 95% CI = 1.03-1.27). There was significant association between LSP1 rs3817198T>C polymorphism and breast cancer risk in BRCA1 and BRCA2 positive cohort in all comparison models (the allele contrast model: OR = 1.08, 95% CI = 1.03-1.13; CC vs. TT: OR = 1.16, 95% CI = 1.05-1.29; TC vs. TT: OR = 1.09, 95% CI = 1.01-1.16; the dominant model: OR = 1.10, 95% CI = 1.03-1.17; the recessive model: OR = 1.12, 95% CI = 1.01-1.23). In conclusion, this meta-analysis suggests that the LSP1 rs3817198T>C polymorphism is a low-penetrant risk factor for developing breast cancer but may not be in Africans.

This meta-analysis on case-control studies aims to examine whether the p53 Arg72Pro polymorphism is associated with colorectal cancer risk, addressing also whether the effect of the polymorphism is modified by race.

Epidermal growth factor (EGF) plays a key role in survival of neural and glial precursor cells. The +61A/G polymorphism of the EGF gene is located in the 5'-untranslated region of EGF mRNA and may affect DNA folding or gene transcription, leading to the increase in EGF protein expression. The association between the +61G allele and glioma risk has been widely reported; however, in general the data from published studies with individually low statistical power were controversial and underpowered. We conducted a search in the PubMed database without a language limitation, covering all papers published by the end of October 2010. Overall, 6 case-control studies with 1453 glioma cases and 1947 controls were retrieved based on the search criteria for glioma susceptibility related to the +61A/G polymorphism. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. We found that EGF +61G allele is associated with the low glioma risk in Chinese population [G-allele vs. A-allele, OR = 0.93, 95%CI (0.89-0.97), P(heterogeneity) = 0.318, I² = 0.0], but with the high glioma risk in European population [G-allele vs. A-allele, OR = 1.14, 95%CI (1.04-1.24), P(heterogeneity) = 0.310, I² = 14.6]. In the stratified analysis by source of control, significant association was observed between hospital-based control and glioma risk [homozygote comparison, OR = 1.14, 95%CI (1.02-1.27), P(heterogeneity) = 0.179, I² = 71.8]. In conclusion, EGF +61G allele represents a risk factor for glioma in European population and conversely a protective factor in Chinese population.

Observed associations of alcohol with colorectal cancer are prone to distortion by confounding and reverse causation. A Mendelian randomization approach provides an unbiased estimate of the association using the aldehyde dehydrogenase 2 (ALDH2) variant as a surrogate of alcohol exposure.

TNF-α-308 G/A, TNF-α-238 G/A, IL-1B-31 T/C, IL-1B-511 C/T, and IL-10-1082 G/A polymorphisms have been reported to influence the risk for hepatocellular carcinoma (HCC) in many studies; however, the results still remains controversial and ambiguous. The aim of this study was to determine more precise estimations for the relationship between TNF-α, IL-1B, and IL-10 polymorphisms and the risk for HCC by meta-analysis.