To estimate the risks of ovarian cancer and breast cancer associated with oral contraceptive (OC) use among women at elevated risk owing to mutations in BRCA1/2 or a strong family history.

The diagnostic value of TMPRSS2:ERG detection in patients with prostate cancer is controversial. We performed a meta-analysis to consolidate current evidence regarding the use of TMPRSS2:ERG detection assays to diagnose prostate cancers. PubMed, Web of knowledge and other databases were searched for relevant original articles published until July 30, 2013. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Studies that investigated the presence of TMPRSS2:ERG in the body fluid, needle biopsy and prostatectomy tissue of patients with prostate cancer were identified and reviewed. Sensitivities, specificities, and positive likelihood ratios (LR+) and negative likelihood ratios (LR-) of TMPRSS2:ERG detection in individual studies were calculated and meta-analyzed by random effects model. Thirty-two studies met the inclusion criteria for the meta-analysis. Overall sensitivity of TMPRSS2:ERG detection assays was 47.4% (95% CI, 45.5-49.3%); specificity, LR+, and LR- was 92.6% (95% CI, 91.5-93.7%), 8.94 (95% CI, 5.65-14.13) and 0.49 (95% CI, 0.43-0.55). The pooled sensitivity and specificity in the body fluid subgroup was 44.7% (95% CI, 41.5-47.9 %) and 85.8% (95% CI, 83.5-87.8%), respectively. The pooled sensitivity and specificity based on the reverse transcripts PCR was 49.0% (95% CI, 45.9-52.1%) and 90.2% (95% CI, 88.2-92.0%), respectively. TMPRSS2:ERG may not be used as first-line screening test. However, due to the high specificity, TMPRSS2: ERG detection maybe can serve as a quick and noninvasive method for confirming prostate cancer diagnosis.

PTEN hamartoma tumor syndrome (PHTS) refers to a spectrum of disorders caused by mutations in the phosphatase and tensin homolog (PTEN) gene. Diagnostic criteria for Cowden syndrome, the principal PTEN-related disorder, were first established in 1996 before the identification of the PTEN gene and the ability to molecularly confirm a clinical diagnosis. These consortium criteria were based on clinical experience and case reports in the existing literature, with their inherent selection biases. Although it was initially reported that approximately 80% of patients with Cowden syndrome had an identifiable germline PTEN mutation, more recent work has shown these diagnostic criteria to be far less specific. In addition, increasing evidence has documented the association of a broader spectrum of clinical features with PTEN mutations. Our goal was to develop revised, evidence-based diagnostic criteria and to include features of the broader spectrum of PTEN-related clinical syndromes.

Murine double minute 2 (MDM2) plays an important role in the carcinogenesis of many cancers including osteosarcoma. We performed a systemic review and meta-analysis to assess the effects of MDM2 polymorphisms on osteosarcoma risk and survival of patients with osteosarcoma. PubMed, Web of Science, and Wanfang databases were searched for eligible studies on the associations of MDM2 polymorphisms with osteosarcoma risk and survival of patients with osteosarcoma. Pooled odds ratio (OR) or hazard ratio (HR) with 95 % confidence intervals (95 % CIs) was used to assess the effects of MDM2 polymorphisms on osteosarcoma risk and survival of patients with osteosarcoma. Overall, MDM2 rs2279744 polymorphism was associated with a risk of osteosarcoma (allele model, OR = 1.60, 95 % CI 1.23-2.07, P < 0.001; codominant model, OR = 2.47, 95 % CI 1.46-4.19, P = 0.001; recessive model, OR = 2.13, 95 % CI 1.32-3.46, P = 0.002; dominant model, OR = 1.61, 95 % CI 1.12-2.33, P = 0.01). MDM2 rs1690916 polymorphism was also associated with a risk of osteosarcoma (OR = 0.60, 95 % CI 0.46-0.77, P < 0.001). However, MDM2 rs2279744 polymorphism was not associated with the overall survival of patients with osteosarcoma (codominant model, HR = 1.01, 95 % CI 0.53-1.91, P = 0.98; recessive model, HR = 1.07, 95 % CI 0.54-2.11, P = 0.85; dominant model, HR = 1.04, 95 % CI 0.65-1.66, P = 0.87). The meta-analysis suggests that MDM2 polymorphisms have some effects on the risk of osteosarcoma but have no effect on the survival of patients with osteosarcoma. Future studies are needed to further assess the effects of MDM2 polymorphisms on the risk and survival of osteosarcoma.

Despite the advances made in cancer management over the past few decades, improvements in cancer diagnosis and prognosis are still poor, highlighting the need for individualized strategies. Toward this goal, risk prediction models and molecular diagnostic tools have been developed, tailoring each step of risk assessment from diagnosis to treatment and clinical outcomes based on the individual's clinical, epidemiological, and molecular profiles. These approaches hold increasing promise for delivering a new paradigm to maximize the efficiency of cancer surveillance and efficacy of treatment. However, they require stringent study design, methodology development, comprehensive assessment of biomarkers and risk factors, and extensive validation to ensure their overall usefulness for clinical translation. In the current study, the authors conducted a systematic review using breast cancer as an example and provide general guidelines for risk prediction models and molecular diagnostic tools, including development, assessment, and validation.

Colorectal cancer is a heterogeneous disease with multiple underlying genetic mutations resulting in different phenotypes. Mutation in the v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) proto-oncogene is an important event in the methylator pathway. There is no consensus, however, on the clinicopathological characteristics associated with BRAF mutation.

To evaluate evidence on the association between CYP2D6 genotype and tamoxifen response through.

Gene expression profiling (GEP) and expanded immunohistochemistry (IHC) tests aim to improve decision-making relating to adjuvant chemotherapy for women with early breast cancer.

The roles of miRNAs in human diseases are emerging. Manipulation of miRNA expression seems to be an effective approach to control disease severity. It has recently been found that Toll-like receptors and miRNAs work by exerting reciprocal effects. Toll-like receptor stimulation can lead to up-/down-regulation of various miRNA expressions. Lipopolysaccharide induction may result in interactions between different miRNAs. Several miRNAs are involved in cancers, indicating the importance of identifying strategies to properly manipulate their expression level. The control of various miRNA expression levels, taking into consideration the plethora of their target genes and the possibility that this may lead to contracting function, which is an important issue in treatment of any miRNA-based (phenotype) disease.

Prostate cancer (PCa) remains as one of the most common cause of cancer related death among men in the US. The widely used prostate specific antigen (PSA) screening is limited by low specificity. The diagnostic value of other biomarkers such as RAS association domain family protein 1 A (RASSF1A) promoter methylation in prostate cancer and the relationship between RASSF1A methylation and pathological features or tumor stage remains to be established. Therefore, a meta-analysis of published studies was performed to understand the association between RASSF1A methylation and prostate cancer. In total, 16 studies involving 1431 cases and 565 controls were pooled with a random effect model in this investigation. The odds ratio (OR) of RASSF1A methylation in PCa case, compared to controls, was 14.73 with 95% CI = 7.58-28.61. Stratified analyses consistently showed a similar risk across different sample types and, methylation detection methods. In addition, RASSF1A methylation was associated with high Gleason score OR=2.35, 95% CI: 1.56-3.53. Furthermore, the pooled specificity for all included studies was 0.87 (95% CI: 0.72-0.94), and the pooled sensitivity was 0.76 (95% CI: 0.55-0.89). The specificity in each subgroup stratified by sample type remained above 0.84 and the sensitivity also remained above 0.60. These results suggested that RASSF1A promoter methylation would be a potential biomarker in PCa diagnosis and therapy.

The role of hypoxia-inducible factors-1 alpha (HIF-1α) expression in gastric cancer remains controversial. We performed a systematic review of the literature with meta-analysis. Electronic databases were used to identify published studies before December 1, 2012. Pooled hazard ratio (HR) or odds ratio (OR) with 95 % confidence interval (95 % CI) was used to estimate the strength of the association between HIF-1α expression and survival of gastric cancer patients. Heterogeneity and publication bias were also assessed. Final analysis of 1,268 patients from 9 eligible studies was performed. High HIF-1α expression was significantly correlated with poor overall survival (OS) of gastric cancer patients (HR = 2.14, 95 % CI = 1.32-3.48). Subgroup analysis indicated that HIF-1α over-expression had an unfavorable impact on OS in Asian patients (HR = 2.35, 95 % CI = 1.41-3.92). Moreover, up-regulation of HIF-1α was significantly associated with the depth of invasion (OR = 2.49, 95 % CI = 1.28-4.83), lymph node metastasis (OR = 2.15, 95 % CI = 1.27-3.66), and vascular invasion (OR = 2.23, 95 % CI = 1.20-4.14). HIF-1α expression might be a predicative factor of poor prognosis for gastric cancer particularly in Asia.

Overexpression of the human papillomavirus (HPV) oncogenes E6 and E7 is necessary for the development of distinct lower genital tract cancers. However, secondary cellular genomic alterations are mandatory to promote progression of HPV-induced premalignant stages. We aimed at identifying the chromosomal regions most frequently gained and lost and the disease stage at which the latter occurs. These regions might be relevant for carcinogenesis and could serve as diagnostic markers to identify premalignant lesions with high progression risk towards invasive cancer.

Melanoma is a very aggressive skin cancer with increasing incidence worldwide. MicroRNAs are small, noncoding RNAs that regulate gene expression of targeted gene(s). The hallmark of cancer model outlined by Hanahan and Weinberg offers a meaningful framework to consider the roles of microRNAs in melanoma development and progression. In this systematic review of the literature, we associate what is known about deregulation of microRNAs and their targeted genes in melanoma development with the hallmarks and characteristics of cancer. The diagnostic and therapeutic potential of microRNAs for future melanoma management will also be discussed.

Epidemiological studies have assessed the association between HIF-1α polymorphisms and cancer risk. However, the results remained conflicting rather than conclusive. Therefore, we performed a systematic review to provide a complete picture and conducted a meta-analysis to derive a precise estimation. We searched PubMed, Embase, and China National Knowledge Infrastructure (CNKI) databases until July 2013 to identify eligible studies. Data sets (43) from 39 studies with a total of 10,841 cases and 14,682 controls were included. The most commonly investigated polymorphism was C1772T, followed by G1790A, C111A, and rs2057482. Overall, C1772T and G1790A but not rs2057482 were associated with increased risk for cancer. When stratified by cancer type, C1772T was associated with increased risk for cervical cancer (T/T vs. C/T+C/C: OR = 8.80, 95 % CI = 2.30-33.70), prostate cancer (T vs. C: OR = 1.54, 95 % CI = 1.04-2.30), and other cancers (T vs. C: OR = 1.42, 95 % CI = 1.07-1.89), but not oral, breast, colorectal, endometrial, lung, and bladder cancers or renal cell carcinoma. G1790A was associated with marginal but insignificant risk for prostate cancer (A vs. G: OR = 1.46, 95 % CI = 1.00-2.13, P = 0.056) and with increased risk for oral (A vs. G: OR = 9.66, 95 % CI = 1.31-71.15), lung (A vs. G: OR = 2.27, 95 % CI = 1.74-2.96), and other cancers (A vs. G: OR = 2.06, 95 % CI = 1.26-3.37) and renal cell carcinoma (A/A vs. G/A+G/G: OR = 3.05, 95 % CI = 1.36-6.84), but not breast, colorectal, cervical, or bladder cancer. Furthermore, we detected increased cancer risk in haplotypes TA and CA and in those carrying at least one risk allele, and decreased cancer risk in haplotype TG regarding C1772T and G1790A polymorphisms. Further well-designed studies on various cancer types are warranted to verify our findings.

Gastric cancer (GC) remains a major cause of morbidity and mortality worldwide and there is therefore a clear need to search for more sensitive early diagnostic biomarkers. We performed a systematic review of eight published miRNA profiling studies that compared GC tissues with adjacent noncancerous tissues. A miRNA ranking system was used that took the frequency of comparisons, direction of differential expression and total sample size into consideration. We identified five miRNAs that were most consistently reported to be upregulated (miR-21, miR-106b, miR-17, miR-18a and miR-20a) and two miRNAs that were downregulated (miR-378 and miR-638). Six of these were further validated in 32 paired sets of GC and adjacent noncancerous tissue samples using real-time PCR. MiR-21, miR-106b, miR-17, miR-18a and miR-20a were confirmed to be upregulatedin GC tissues, while the expression of miR-378 was decreased. Moreover, we found a significant association between expression levels of miR-21, miR-106b, miR-17, miR-18a and miR-20a and clinicopathological features of GC. These miRNAs may be used for diagnostic and/or prognostic biomarkers for GC and therefore warrant further investigation.

Reactive oxygen species-related damage plays a critical role in carcinogenesis. Glutathione peroxidase 1 (GPX1) and mitochondrial superoxide dismutase (MnSOD) are two key antioxidant enzymes in the defense system against reactive oxygen species. This systematic review and meta-analysis was designed to evaluate the association of single-nucleotide polymorphisms in GPX1 and MnSOD genes with susceptibility to bladder cancer risk. Online databases of PubMed, Embase, China National Knowledge Infrastructure, and SinoMed were searched to identify eligible studies. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to estimated the association strength. The fixed effects model and random effects model were used to pool the data from different studies. By pooling all eligible studies, we found that the GPX1 Pro198Leu polymorphism was associated with a significantly increased risk of bladder cancer (Leu vs. Pro, OR = 2.111, 95% CI = 1.020-4.368, heterogeneity (p < 0.001); LeuPro/LeuLeu vs. ProPro, OR = 1.876, 95% CI = 1.011-3.480, heterogeneity (p < 0.001)). No significant association of MnSOD Ala-9Val polymorphism with cancer risk was observed (AlaVal/ValVal vs. AlaAla, OR = 0.966, 95% CI = 0.754-1.239, heterogeneity (p = 0.390); Vla vs. Ala, OR = 1.038, 95% CI = 0.782-1.377, heterogeneity (p = 0.015)). This systematic review and meta-analysis demonstrated that the GPX1 Pro198Leu polymorphism significantly increased susceptibility to bladder cancer, while the MnSOD Ala-9Val polymorphism was not associated with bladder cancer risk.

Osteosarcoma is the most common malignant bone tumor, and the prognosis of patients with osteosarcoma is still unsatisfactory with low survival rates. There are many studies assessing the prognostic role of upregulated p53 in patients presenting osteosarcoma, and there is no consistent finding. To summarize the existing evidence about whether the presence of upregulated p53 was a biomarker of survival in patients with osteosarcoma, we performed a systematic review and meta-analysis of relevant publications. We assessed the effect of upregulated p53 on the 3-year overall survival and the 3-year disease-free survival by calculating the pooled odds ratio (OR) with corresponding 95% confidence interval (95%CI). Fifteen studies with a total of 609 patients with osteosarcoma were finally included into the systematic review and meta-analysis. Compared with osteosarcoma patients with low or undetectable p53, patients with upregulated p53 were obviously associated with decreased 3-year overall survival (OR = 0.29, 95 %CI 0.19-0.43, P < 0.001). In addition, patients with upregulated p53 were obviously associated with decreased 3-year disease-free survival (OR = 0.06, 95 %CI 0.02-0.23, P < 0.001). The results from the systematic review and meta-analysis highlight that p53 is an effective biomarker of survival in patients with osteosarcoma. In addition, more studies with a large sample size are needed to identify the effect of p53 expression in osteosarcoma patients.

Published studies researching the prognostic significance of ezrin expression in patients with osteosarcoma are inconclusive and heterogeneous. We conducted a meta-analysis to assess its prognostic value more precisely. The hazard ratios with corresponding 95 % confidence intervals were calculated to evaluate the effects. Five studies with 318 osteosarcoma patients were included to estimate the relationship between ezrin and disease-free survival, and ezrin and overall survival. Compared with osteosarcoma patients with low or negative ezrin expression, patients with high ezrin expression tended to be associated with lower disease-free survival, but the difference was not significant. However, patients with high ezrin expression were obviously associated with lower overall survival. Therefore, the findings from this systematic review suggest that ezrin expression is an effective biomarker of prognosis in patients with osteosarcoma.

Previous published data on the association between X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism and clinical outcome of platinum-based chemotherapy in patients with lung cancer reported conflicting results. A meta-analysis was performed to provide a systematic review of the published data. We retrieved the relevant studies from PubMed and Embase databases. The primary outcome was overall survival, and the hazard ratio (HR) with 95% confidence interval (95% CI) was estimated. Seven studies with a total of 1,514 patients were included into the meta-analysis. Overall, XRCC3 Thr241Met polymorphism had no influence on the overall survival of lung cancer patients receiving platinum-based chemotherapy (MetMet vs. ThrThr: HR = 0.82, 95% CI 0.52-1.31, P = 0.410; MetThr vs. ThrThr: HR = 0.93, 95% CI 0.79-1.10, P = 0.339; MetMet/MetThr vs. ThrThr: HR = 1.07, 95% CI 0.88-1.31, P = 0.480). There was no obvious risk of publication bias. Therefore, currently available data suggest that there is no predictive effect of XRCC3 Thr241Met polymorphism on platinum-based chemotherapy in lung cancer patients.

The correlation between xeroderma pigmentosum group D (XPD) polymorphisms (Lys751Gln and Asp312Asn) and clinical outcomes of non-small cell lung cancer (NSCLC) patients, who received platinum-based chemotherapy (Pt-chemotherapy), is still inconclusive. This meta-analysis was aimed to systematically review published evidence and ascertain the exact role of XPD polymorphisms.