Studies investigating the associations between tumor necrosis factor-alpha (TNFA) polymorphisms and hepatocellular carcinoma (HCC) risk report conflicting results. We conducted a meta-analysis to assess the association between TNFA gene TNFA-308(G/A), TNFA-238(G/A), TNFA-863(C/A), TNFA-857(C/T), TNFA-1031 (T/C) polymorphisms and HCC susceptibility.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) are effective as first-line treatment of advanced non-small-cell lung cancer patients with EGFR mutations (EGFR-M+).

Published data on the association between three polymorphisms (Lys939Gln, Ala499Val, and PAT±) of Xeroderma Pigmentosum group C (XPC) and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between them. A total of 11 studies including 5,090 cases and 5,214 controls were involved in this meta-analysis. For XPC Lys939Gln polymorphism, no obvious associations were found for all genetic models when all studies were pooled into the meta-analysis (Lys/Gln vs. Lys/Lys: OR = 1.00, 95% CI 0.92-1.10; Gln/Gln vs. Lys/Lys: OR = 0.96, 95% CI 0.84-1.09; dominant model: OR = 0.99, 95% CI 0.91-1.08; and recessive model: OR = 0.97, 95% CI 0.86-1.09). In the subgroup analysis by ethnicity or study design, still no obvious associations were found. For XPC Ala499Val polymorphism, also no obvious associations were found for all genetic models when all studies were pooled into the meta-analysis (Val/Ala vs. Ala/Ala: OR = 0.91, 95% CI 0.79-1.05; Val/Val vs. Ala/Ala: OR = 1.07, 95% CI 0.80-1.44; dominant model: OR = 0.93, 95% CI 0.81-1.06; and recessive model: OR = 1.11, 95% CI 0.84-1.48). For XPC PAT± polymorphism, obvious associations were found for recessive model when all studies were pooled into the meta-analysis (OR = 1.41, 95% CI 1.05-1.89). In conclusion, this meta-analysis suggests that the XPC PAT± polymorphism allele may be a low-penetrant risk factor for developing breast cancer.

Colorectal cancer (CRC), the most lethal long-term complication of inflammatory bowel disease (IBD), is the culmination of a complex sequence of molecular and histologic derangements of the colon epithelium that are initiated and at least partially sustained by prolonged chronic inflammation. Dysplasia, the earliest histologic manifestation of this process, plays an important role in cancer prevention by providing the first clinical alert that this sequence is under way and by serving as an endpoint in colonoscopic surveillance of patients at high risk for CRC. Restorative proctocolectomy (RPC) is indicated for patients with IBD, specifically for ulcerative colitis that is refractory to medical treatment, emergency conditions, and/or in case of neoplastic transformation. Even after RPC with mucosectomy, pouch-related carcinomas have recently been reported with increasing frequency since the first report in 1984. We review IBD-associated CRC and pouch-related neoplasia prevalence, adverse events, risk factors, and surveillances.

Esophageal cancer (EC) is one of the most common cancers worldwide with 5-year survival rate less than 10%. However, there is a lack of specific genetic markers that could help better understanding the mechanisms of esophageal carcinogenesis, improving the detection rate of EC, and distinguishing histological types. Cyclooxygenase-2 (COX-2) as an inducible enzyme in cancer development and progression is involved in esophageal carcinogenesis. A large number of studies have demonstrated a strong association between COX-2 polymorphisms and EC risk. However, the overall results are still controversial. This controversy may be partly due to the mix-up of esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EAC). The aim of this study was to investigate the association between COX-2 polymorphisms and susceptibility to ESCC or EAC by conducting a meta-analysis. Seven studies were retrieved reporting a total of 1450 ESCC patients, 523 EAC patients, and 2663 cancer-free control subjects. Five COX-2 polymorphisms were addressed, including -765G>C (rs20417), -1195G>A (rs689465), -1290A>G (rs689466), -8473T>C (rs5275) and -1759G>A (rs3218625). Meta-analysis results showed that the -765C allele is significantly associated with the susceptibility to both ESCC and EAC especially in Asian populations. In addition, there was a significant association between the -8473C allele and the susceptibility to EAC in Caucasian populations. In conclusion, our meta-analysis suggests that the -765C allele of the COX-2 gene might be a potential risk factor for both ESCC and EAC especially in Asian populations, while the -8473C allele might be a risk factor for EAC in Caucasian populations.

Identification of novel biomarkers of cancer is important for improved diagnosis, prognosis, and therapeutic intervention. This study aimed to identify marker genes of colorectal cancer (CRC) by combining bioinformatics analysis of gene expression data and validation experiments using patient samples and to examine the potential connection between validated markers and the established oncogenes such as c-Myc and K-ras.

The bioenergetic status of non-small cell lung cancer correlates with tumour aggressiveness. The voltage dependent anion channel type 1 (VDAC1) is a component of the mitochondrial permeability transition pore, regulates mitochondrial ATP/ADP exchange suggesting that its over-expression could be associated with energy dependent processes including increased proliferation and invasiveness. To test this hypothesis, we conducted an in vivo gene-expression meta-analysis of surgically resected non-small cell lung cancer (NSCLC) using 602 individual expression profiles, to examine the impact of VDAC1 on survival.

DNA repair genes are important for maintaining genomic stability and limiting carcinogenesis. We analyzed all single nucleotide polymorphisms (SNPs) of 125 DNA repair genes covered by the Illumina HumanHap300 (v1.1) BeadChips in a previously conducted genome-wide association study (GWAS) of 1154 lung cancer cases and 1137 controls and replicated the top-hits of XRCC4 SNPs in an independent set of 597 cases and 611 controls in Texas populations. We found that six of 20 XRCC4 SNPs were associated with a decreased risk of lung cancer with a P-value of 0.01 or lower in the discovery dataset, of which the most significant SNP was rs10040363 (P for allelic test=4.89 x 10⁻⁴). Moreover, the data in this region allowed us to impute a potentially functional SNP rs2075685 (imputed P for allelic test=1.3 x 10⁻³). A luciferase reporter assay demonstrated that the rs2075685G>T change in the XRCC4 promoter increased expression of the gene. In the replication study of rs10040363, rs1478486, rs9293329, and rs2075685, however, only rs10040363 achieved a borderline association with a decreased risk of lung cancer in a dominant model (adjusted OR=0.80, 95% CI=0.62-1.03 and P=0.079). In the final combined analysis of both the Texas GWAS discovery and replication datasets, the strength of the association was increased for rs10040363 (adjusted OR=0.77, 95% CI=0.66-0.89, P(dominant)=5 x 10⁻⁴ and P for trend=5 x 10⁻⁴) and rs1478486 (adjusted OR=0.82, 95% CI=0.71-0.94, P(dominant)=6 x 10⁻³ and P for trend=3.5 x 10⁻³). Finally, we conducted a meta-analysis of these XRCC4 SNPs with available data from published GWA studies of lung cancer with a total of 12,312 cases and 47,921 controls, in which none of these XRCC4 SNPs was associated with lung cancer risk. It appeared that rs2075685, although associated with increased expression of a reporter gene and lung cancer risk in the Texas populations, did not have an effect on lung cancer risk in other populations. This study underscores the importance of replication using published data in larger populations.

Tumors of peripheral nerve are largely neuroectodermal in nature and derived from 2 elements of nerve, Schwann or perineurial cells. In contrast, mesenchymal tumors affecting peripheral nerve are rare and are derived mainly from epineurial connective tissue. The spectrum of the latter is broad and includes lipoma, vascular neoplasms, hematopoietic tumors, and even meningioma. Of malignant peripheral nerve neoplasms, the vast majority are primary peripheral nerve sheath tumors. Malignancies of mesenchymal type are much less common. To date, only 12 cases of synovial sarcoma of nerve have been described. Whereas in the past, parallels were drawn between synovial sarcoma and malignant glandular schwannoma, an uncommon form of malignant peripheral nerve sheath tumor, molecular genetics have since clarified the distinction. Herein, we report 10 additional examples of molecularly confirmed synovial sarcoma, all arising within minor or major nerves. Affecting 7 female and 3 male patients, 4 tumors occurred in pediatric patients. Clinically and radiologically, most lesions were initially thought to be benign nerve sheath tumors. On reinterpretation of imaging, they were considered indeterminate in nature with some features suspicious for malignancy. Synovial sarcoma of nerve, albeit rare, seems to behave in a manner similar to its more common, soft tissue counterpart. Those affecting nerve have a variable prognosis. Definitive recommendations regarding surgery and adjuvant therapies await additional reports and long-term follow-up. The literature is reviewed and a meta-analysis is performed with respect to clinicopathologic features versus outcome.

N-acetyltransferase 2 (NAT2) gene encodes a key enzyme involved in the metabolism of xenobiotics and whose polymorphisms have been related to individual susceptibility to several malignancies. Although many epidemiological studies have explored the association between NAT2 genetic polymorphism and lung cancer risk, the results remain controversial. In order to assess the overall relationship between NAT2 polymorphism and lung cancer risk, we performed a meta-analysis including 3945 lung cancer cases and 6085 controls from 19 published studies which were selected from 29 articles identified by a search of PubMed up to 1st June 2010. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association. No significant association was found in overall analysis (OR=1.02, 95% CI=0.90-1.16, P=0.01 for heterogeneity) and in subgroup analyses by ethnicity, sex, histological type, smoking status and study design. In conclusion, this meta-analysis found little evidence of an association between the NAT2 polymorphism and the risk of lung cancer.

Individual differences among breast tumours in patients is a significant challenge for the treatment of breast cancer. This study reports a strategy to assess these individual differences and the common regulatory mechanisms that may underlie breast tumourigenesis.

Anti-epidermal growth factor receptor monoclonal antibodies (panitumumab [P] and cetuximab [C]) are approved and effective only in KRAS wild-type patients with advanced colorectal cancer. The purpose of our meta-analysis is to evaluate the real effects of C and P in KRAS wild-type patients treated in randomized trials.

High-percent mammographic density adjusted for age and body mass index is one of the strongest risk factors for breast cancer. We conducted a meta analysis of five genome-wide association studies of percent mammographic density and report an association with rs10995190 in ZNF365 (combined P = 9.6 × 10(-10)). Common variants in ZNF365 have also recently been associated with susceptibility to breast cancer.

Nucleotide excision repair (NER) modulates platinum-based chemotherapeutic efficacy by removing drug-produced DNA damage. To summarize published data on the association between polymorphisms of NER genes (ERCC1 and ERCC2) and responses to oxaliplatin-based chemotherapies, we carried out a meta-analysis of gastric and colorectal cancer for commonly studied polymorphisms ERCC1 rs11615C>T and ERCC2 rs13181T>G.

This meta-analysis aims to examine whether the genotype status of Msp1, Ile462Val, and Thr461Asn polymorphisms in cytochrome P450 1A1 (CYP1A1) is associated with endometrial cancer risk.

The DNA repair protein O6-Methylguanine-DNA methyltransferase (MGMT) confers resistance to alkylating agents. Several methods have been applied to its analysis, with methylation-specific polymerase chain reaction (MSP) the most commonly used for promoter methylation study, while immunohistochemistry (IHC) has become the most frequently used for the detection of MGMT protein expression. Agreement on the best and most reliable technique for evaluating MGMT status remains unsettled. The aim of this study was to perform a systematic review and meta-analysis of the correlation between IHC and MSP.

Inflammatory bowel disease (IBD) and colorectal cancer (CRC) are common health problems worldwide. Tumor necrosis factor (TNF) is a type of cytokine that induces inflammation and inhibits tumorigenesis. Several studies have assessed the relationship between the polymorphism of TNF-α-308 G>A and the susceptibility to IBD and CRC; however, the results have been controversial. In addition, the hypothesis whether the increased risk of CRC in IBD patients could be partly ascribed to the polymorphism of TNF-α-308 G>A was unclear. Therefore, we conducted this meta-analysis to confirm these associations. Pooled odd ratios (ORs) and 95% confidence intervals (95% CIs) were calculated on the basis of data from 14, 18, and 7 studies from a total of 27 studies for the associations between the polymorphism of TNF-α-308 G>A and ulcerative colitis, Crohn's disease (CD) and CRC. In Europeans, the AA genotype increased the risk of ulcerative colitis (UC) (OR, 2.041; 95% CI, 1.261-3.301) and CD (OR, 1.730; 95% CI, 1.168-2.564) significantly, without obvious heterogeneity and publication bias. Meanwhile, the GA genotype increased the risk of UC in Asians (OR, 2.360; 95% CI, 1.269-4.390) significantly. However, no significant association was observed for CRC in any ethnic population. The results of this meta-analysis suggested that the polymorphism of TNF-α-308 G>A participates in modifying the susceptibility to UC and CD in Europeans and Asians. The increased risk of CRC in IBD patients should be clarified as the combined effects of polymorphisms in TNF-α and other cytokines, and the interaction with environmental factors, in future studies.

To study the relation between CYP1A1 Ile462Val polymorphism and colorectal cancer risk by meta-analysis.

Colorectal cancer (CRC) is a multifactorial disease with both environmental and genetic factors contributing to its development. The incidence of CRC is increasing year by year in Japan. Patients with CRC in advanced stages have a poor prognosis, but detection of CRC at earlier stages can improve clinical outcome. Therefore, identification of epidemiologial factors that influence development of CRC would facilitate the prevention or early detection of disease.

Panitumumab is a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody that has a favorable effect on patients with metastatic colorectal cancer (mCRC) harboring wild-type (WT) KRAS gene. This meta-analysis was planned to quantify the benefit and assess safety. Selected for the analysis were randomized clinical studies that have used panitumumab-based therapy (PBT) for patients with mCRC and where the outcome of patients with WT KRAS was reported. Four eligible studies were analyzed including 1,010 and 1,105 patients who received PBT and the control intervention, respectively. Used in subsequent-line setting, PBT was associated with 42% improvement in progression-free survival (PFS) (hazard ratio [HR] = 0.58; 95% CI, 0.36-0.93; P = 0.02), a non-significant overall survival (OS) benefit (HR = 0.90; [95% CI, 0.76-1.05]; P = 0.18), and a significant increase in objective response rate (ORR) (odds ratio (OR) = 0.67 [95% CI, 1.15-77.98]; P = 0.04). PBT showed no benefit in the first-line setting. Restricted analysis to two studies (first- and second-line setting), where the treatment effect of PBT was prospectively analyzed according to tumor KRAS status, showed significant PFS (HR = 0.77), OS (HR = 0.84), and ORR (OR = 2.06) advantage. Almost all patients' subgroups attained clinical benefit. PBT-related adverse events were similar across comparisons with the exception of toxicities known to be associated with anti-EGFR therapy. This meta-analysis showed significant clinical benefit for PBT for patients with WT KRAS mCRC predominantly when used following prior chemotherapy exposure. The benefit was demonstrated in most subgroup analyses. Further research to better define potential responders is needed.