The P53-MDM2 pathway plays a central role in sarcoma pathogenesis. Functional P53 Arg72Pro and MDM2 T309G single-nucleotide polymorphisms (SNP) are considered to have significant effects on risk of sarcomas.

To date, epidemiological studies have assessed the association between Ataxia-telangiectasia mutated (ATM) gene polymorphisms and cancer risk, including lung cancer, breast cancer, glioma and pancreatic cancer. However, the results of these studies remain controversial. We aimed to examine the associations between two SNPs (rs664143 and rs664677) and cancer risk by conducting a meta-analysis of case-control studies. A total of 12 publications were included in this meta-analysis, 8 for rs664143 and 7 for rs664677. Overall, rs664143 heterozygote carriers turned out to be associated with cancer risk (OR = 1.18, 95% CI 1.02-1.36). In the subgroup analysis by cancer type, we observed that the ATM rs664143 polymorphism was significantly associated with lung cancer risk (GA vs. GG: OR = 1.48, 95% CI 1.18-1.85, AA vs. GG: OR = 1.51, 95% CI 1.18-1.93) and rs664677 polymorphism was associated with decreased lung cancr risk and increased breast cancer risk (for lung cancer: TC vs. TT: OR = 0.76, 95% CI 0.62-0.92, CC vs. TT: OR = 0.80, 95% CI 0.64-0.99 and for breast cancer: TC vs. TT: OR = 1.42, 95% CI 1.17-1.73, CC vs. TT: OR = 1.51, 95% CI 1.21-1.87). In the subgroup analysis by region, we also observed that individuals with ATM rs664143 GA or AA genotype had an obvious increased cancer risk among Asian people (GA vs. GG: OR = 1.40, 95% CI 1.20-1.63, AA vs. GG: OR = 1.37, 95% CI 1.16-1.62). In conclusion, ATM rs664143 polymorphism was associated with cancer susceptibility. ATM rs664143 polymorphism was significantly associated with lung cancer risk. ATM rs664677 polymorphism was associated with decreased lung cancer risk as well as increased breast cancer risk.

Polymorphisms in PTPN22 are associated with many autoimmune diseases; while rs2476601 is supposed to play a major role, other experimental data suggest that rs2488457 may be even more important. Results in myasthenia gravis are controversial. In 356 Italian myasthenic patients and 439 controls genotyped for both polymorphisms, we found that rs2476601 was not associated with myasthenia, presence of autoantibodies, thymus pathology, sex or onset age unlike previous studies on other European populations (confirmed by the present meta-analysis). On the other hand, while rs2488457 was not associated with myasthenia or thymus pathology, we found a correlation of rs2488457 with low autoantibody titers and a trend of association with a less severe disease. Both polymorphisms were in tight linkage disequilibrium in controls, not in patients. Our results suggest that SNPs in this gene different from rs2476601, and/or epigenetic interactions, could play a greater role.

Prostate cancer is one of the most common male malignant neoplasms; however, its causes are not completely understood. A few recent studies have used gene expression profiling of prostate cancer to identify differentially expressed genes and possible relevant pathways. However, few studies have examined the genetic mechanics of prostate cancer at the pathway level to search for such pathways. We used gene set enrichment analysis and a meta-analysis of six independent studies after standardized microarray preprocessing, which increased concordance between these gene datasets. Based on gene set enrichment analysis, there were 12 down- and 25 up-regulated mixing pathways in more than two tissue datasets, while there were two down- and two up-regulated mixing pathways in three cell datasets. Based on the meta-analysis, there were 46 and nine common pathways in the tissue and cell datasets, respectively. Three up- and 10 down-regulated crossing pathways were detected with combined gene set enrichment analysis and meta-analysis. We found that genes with small changes are difficult to detect by classic univariate statistics; they can more easily be identified by pathway analysis. After standardized microarray preprocessing, we applied gene set enrichment analysis and a meta-analysis to increase the concordance in identifying biological mechanisms involved in prostate cancer. The gene pathways that we identified could provide insight concerning the development of prostate cancer.

Studies investigating the association between cytochrome P450 1B1 (CYP1B1) Leu432Val (432 C/G, rs1056836) polymorphism and colorectal cancer (CRC) risk report conflicting results. The aim of this study was to quantitatively summarize the evidence for such a relationship. Two investigators independently searched the Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine Databases. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for CYP1B1 polymorphism and CRC were calculated in a fixed-effects model and a random-effects model when appropriate. The pooled ORs were performed for co-dominant model (GG vs. CC, GC vs. CC), dominant model (GG + GC vs. CC), and recessive model (GG vs. GC + CC). This meta-analysis included ten case-control studies, which included 8,466 CRC cases and 9,301 controls. Overall, the variant genotypes (GG and GC) of the 432 C/G were not associated with CRC risk when compared with the wild-type CC homozygote (GG vs. CC, OR = 1.01, 95% CI = 0.93-1.10; GC vs. CC, OR = 0.97, 95% CI = 0.90-1.04), without any between-study heterogeneity. Similarly, no associations were found in the dominant and recessive models (dominant model, OR = 0.98, 95% CI = 0.92-1.05; recessive model, OR = 1.03, 95% CI = 0.96-1.11). Limiting the analysis to the studies within Hardy-Weinberg equilibrium, the results were persistent and robust. When stratifying for country, matched control and source of controls, no evidence of significant association was observed in any subgroup. No publication bias was found in the present study. No association is found between the CYP1B1 Leu432Val polymorphism and risk of CRC among Caucasians.

The cytokinesis-block micronucleus test (MNT), as a marker of chromosomal mutagen sensitivity, was applied in a number of studies enrolling breast cancer (BC) patients and subjects with known or putative genetic predisposition to BC. The large majority of them involve the evaluation of induced micronuclei (MN) frequency in peripheral lymphocytes, after the in vitro challenge with ionising radiations.

Several studies have investigated the association between Lys751Gln polymorphism in the xeroderma pigmentosum group D (XPD) gene and risk of head and neck cancer; however, the published results are conflicting. We conducted a meta-analysis that comprised 15 published case-control studies examining the association of head and neck cancer risk with XPD Lys751Gln polymorphism in different populations, based on the data identified in Medline up to November 2010. Odds ratios (ORs) with 95% confidence intervals (CI) were used to assess the strength of the association. Overall, significantly elevated head and neck cancer risk was associated with XPD Lys751Gln polymorphism when all studies were pooled into the meta-analysis [(Gln/Gln + Lys/Gln) vs Lys/Lys: OR = 1.12, 95%CI = 1.03-1.22, P < 0.01, heterogeneity P = 0.11]. In the subgroup analysis by ethnicity, borderline significantly increased risk was found for Europeans [(Gln/Gln + Lys/Gln) vs Lys/Lys: OR = 1.11, 95%CI = 1.00-1.23, P < 0.05]. In conclusion, our meta-analysis demonstrated that XPD Lys751Gln polymorphism could be a prediction marker for risk of head and neck cancer.

We examined whether p53 codon 72 polymorphism confers prostate cancer risk by conducting a meta-analysis. Two investigators independently searched the Pubmed, Embase and CBM databases. This meta-analysis was made of seven case-control studies, that included 892 prostate cancer cases and 1020 healthy controls. Meta-analysis results based on all the studies showed no significant association between p53 codon 72 polymorphism and prostate cancer risk in the comparisons of Pro allele vs Arg allele; Pro/Pro + Pro/Arg vs Arg/Arg; Pro/Pro vs Pro/Arg + Arg/Arg; Pro/Pro vs Arg/Arg, and Pro/Arg vs Arg/Arg [odds ratio (OR) = 1.09, 95% confidence interval (CI) = 0.87-1.36, P = 0.47; OR = 1.22, 95%CI = 0.86-1.73, P = 0.27; OR = 1.03, 95%CI = 0.62-1.72, P = 0.91; OR = 1.22, 95%CI = 0.66-2.26, P = 0.52; OR = 1.25, 95%CI = 0.84-1.87, P = 0.27, respectively]. In the subgroup analysis by ethnicity, no association was found between p53 codon 72 polymorphism and prostate cancer risk both in Caucasian and Asian populations. We found no association between p53 codon 72 polymorphism and prostate cancer risk.

Oral squamous cell carcinoma (OSCC) is the sixth most common type of carcinoma worldwide. The pathogenic pathways involved in this cancer are mostly unknown; therefore, a better characterization of the OSCC gene expression profile would represent a considerable advance. The public availability of gene expression datasets was meant to obtain new insights on biological processes.

Cholangiocarcinoma is a heterogeneous disease with a poor outcome that accounts for 5%-10% of primary liver cancers. We characterized its genomic and genetic features and associated these with patient responses to therapy.

APE1 (apurinic/apyrimidinic endonuclease 1) is an important DNA repair protein in the base excision repair pathway. Polymorphisms in APE1 have been implicated in susceptibility to cancer; however, results from the published studies remained inconclusive. The objective of this study was to conduct a meta-analysis investigating the association between polymorphisms in APE1 and the risk for cancer.

To compare the genomic signatures of wild-type (WT) and mutated GISTs and the murine interstitial cells of Cajal (ICCs) to find markers of cell differentiation and other functions that may identify cells that give rise to WT tumours.

Aberrant methylation of promoter DNA and transcriptional repression of specific tumor suppressor genes play an important role in carcinogenesis. Recently, many studies have investigated the association between cigarette smoking and p16(INK4α) gene hypermethylation in lung cancer, but could not reach a unanimous conclusion.

The development and progression of hepatocellular carcinoma (HCC) is significantly correlated to the accumulation of genomic alterations. Array-based comparative genomic hybridization (array CGH) has been applied to a wide range of tumors including HCCs for the genome-wide high resolution screening of DNA copy number changes. However, the relevant chromosomal variations that play a central role in the development of HCC still are not fully elucidated.

BMP4 rs4444235 is a candidate susceptibility allele that has been associated with an increased risk of colorectal cancer. This study was conducted to examine the association between BMP4 rs4444235 polymorphism and colorectal cancer risk. Odds ratio (ORs) with 95% CIs was pooled as effect indicator. A comprehensive search of related publications was conducted and those which met the inclusion criteria were included. Test of heterogeneity, meta-regression, subgroup analysis, cumulative meta-analysis, assessment of publication bias, and sensitivity test were performed using Stata 11.0. 8 articles on rs4444235 including 19,893 cases and 22,106 controls were included. There was slight heterogeneity which may come from ethnicity and source of control. Pooled results for all five genetic models were statistically significant. ORs were 1.063 (95% CI = (1.034, 1.092)), 1.081 (95% CI = (1.028, 1.136)), and 1.166(95% CI = (1.081, 1.258)) for C versus T, TC versus TT, and CC versus TT comparisons respectively. In Caucasian population, carriers of C allele, CC genotype and TC genotype were at an increased risk of developing CRC, with an OR of 1.079 (95% CI = (1.044, 1.114)), 1.095 (95% CI = (1.034, 1.159)), and 1.199 (95% CI = (1.117,1.287)) respectively. Cumulative meta-analysis indicated that pooled ORs were approximating 1.1 with publication year passing. No significant publication bias was suggested. Sensitivity test indicated stable results. In conclusion, BMP4-rs4444235 polymorphism is probably associated with CRC risk, and C allele is a possible risk factor in overall population. The same conclusion was drawn in Caucasians, but no significant results were obtained in other ethnic populations probably due to limited sample sizes.

Published data on the association of vascular endothelial growth factor (VEGF) -1154G>A polymorphism with cancer risk is inconclusive. To derive a more precise estimation of association between VEGF -1154G>A polymorphism and the risk of cancer, we performed a meta-analysis of 7,071 cancer cases and 7,693 controls from 16 published case-control studies. Our meta-analysis didn't reveal an association between VEGF -1154G>A polymorphism and overall cancer risk (GG vs. AA: OR: 1.08, 95% CI: 0.96-1.20; GA vs. AA: OR: 1.04, 95% CI: 0.93-1.17; recessive model: GG+GA vs. AA: OR: 1.06, 95% CI: 0.95-1.18; dominant model: GG vs. GA+AA, OR: 1.11, 95% CI: 1.00-1.24). Nevertheless, for non-Caucasians, GG homozygote may have higher cancer risk compared with either A carriers (OR: 1.58, 95% CI: 1.12-2.23) or AA homozygote (OR: 1.43, 95% CI: 1.17-1.76). No significant heterogeneity was detected except in the dominant model and "prostate cancer" subgroup analysis. More studies with larger samples are warranted to confirm these findings.

Prostate cancer is the most common cancer diagnosis in men and a leading cause of death. Improvements in disease management would have a significant impact and could be facilitated by the development of biomarkers, whether for diagnostic, prognostic, or predictive purposes. The blood-based prostate biomarker PSA has been part of clinical practice for over two decades, although it is surrounded by controversy. While debates of usefulness are ongoing, alternatives should be explored. Particularly with recent recommendations against routine PSA-testing, the time is ripe to explore promising biomarkers to yield a more efficient and accurate screening for detection and management of prostate cancer. Epigenetic changes, more specifically DNA methylation, are amongst the most common alterations in human cancer. These changes are associated with transcriptional silencing of genes, leading to an altered cellular biology.

Gefiinib and erlotinib are two similar small molecules of selective and reversible epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), which have been approved for second-line or third-line indication in previously treated advanced Non-small-cell lung cancer (NSCLC) patients. The results of comparing the EGFR-TKI with standard platinum-based doublet chemotherapy as the first-line treatment in advanced NSCLC patients with activated EGFR mutation were still controversial. A meta-analysis was performed to derive a more precise estimation of these regimens. Finally, six eligible trials involved 1,021 patients were identified. The patients receiving EGFR-TKI as front-line therapy had a significantly longer progression-free survival (PFS) than patients treated with chemotherapy [median PFS was 9.5 versus 5.9 months; hazard ratio (HR)=0.37; 95% confidence intervals (CI)=0.27-0.52; p<0.001]. The overall response rate (ORR) of EGFR-TKI was 66.60%, whereas the ORR of chemotherapy regimen was 30.62%, which was also a statistically significant favor for EGFR-TKI [relative risk (RR)=5.68; 95% CI=3.17-10.18; p<0.001]. The overall survival (OS) was numerically longer in the patients received EGFR-TKI than patients treated by chemotherapy, although the difference did not reach a statistical significance (median OS was 30.5 vs. 23.6 months; HR=0.94; 95% CI=0.77-1.15; p=0.57). Comparing with first-line chemotherapy, treatment of EGFR-TKI achieved a statistical significantly longer PFS, higher ORR and numerically longer OS in the advanced NSCLC patients harboring activated EGFR mutations, thus, it should be the first choice in the previously untreated NSCLC patients with activated EGFR mutation.

The previous published data on the association between X-ray repair cross-complementing group 3 (XRCC3) T241M, A4541G, and A17893G polymorphisms and breast cancer risk remained controversial. Hence, we performed a meta-analysis to investigate the association between breast cancer and XRCC3 T241M (21,910 cases and 23,961 controls), A4541G (9,633 cases and 10,994 controls), and A17893G polymorphisms (10,761 cases and 12,235 controls) in different inheritance models. When all the eligible studies were pooled into the meta-analysis of XRCC3 T241M polymorphism, significantly increased risk of breast cancer was observed in recessive model (odds' ratio [OR] = 1.10, 95% confidence interval [CI] = 1.04-1.16) and in additive model (OR = 1.10, 95% CI = 1.03-1.16). No significant association was found between A4541G polymorphism and breast cancer risk. When all the eligible studies were pooled into the meta-analysis of XRCC3 A17893G polymorphism, no significant association was found in any genetic model. Additionally, when one study was deleted in the sensitive analysis, the results of XRCC3 A17893G were changed in the additive model (OR = 0.90, 95% CI = 0.82-0.99) and dominant model (OR = 0.94, 95% CI = 0.89-0.99). In summary, this meta-analysis indicates that T241M polymorphism show an increased breast cancer risk and A17893G polymorphism may be associated with decreased breast cancer risk. A study with the larger sample size is needed to further evaluated gene-environment interaction on XRCC3 T241M, A4541G, and A17893G polymorphisms and breast cancer risk.