K-RAS gene mutations have been found in 20-30% of non-small cell lung cancer and occur most commonly in adenocarcinoma, however, there was no definitive conclusion about the prognostic role of K-RAS mutations in NSCLC. Herein we performed a systematic review of the literatures with meta-analysis to assess K-RAS mutations' prognostic value in NSCLC. After a methodological assessment, survival data from published studies were aggregated. Combined hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated in terms of overall survival. 41 trials (6939 patients) were included in the analysis, the overall HR was 1.45 (95% CI: 1.29-1.62), showing that K-RAS mutations have an unfavorable impact on survival of patients with NSCLC. Then a subgroup analysis was performed about ethnicity, the combined HR was 1.97 (95% CI: 1.58-2.44) for Asians, and 1.37 (95% CI: 1.25-1.5) for non-Asians. In subgroup analysis of histology, the HR was 1.39 (95% CI: 1.24-1.55) for adenocarcinoma, suggesting that K-RAS mutations were correlated with shortened survival for adenocarcinoma. When the subgroup analysis was conducted according to disease stage, K-RAS mutations were poor prognostic factors in early stages: stage I (1.81; 95% CI: 1.36-2.39) and stage I-IIIa (1.68; 95% CI: 1.11-2.55), but not in advanced stage (IIIb-IV) (1.3; 95% CI: 0.99-1.71). At last, in subgroup analysis about test methods, all of the four methods: PCR-MSOP (1.73; 95% CI: 1.35-2.2), PCR-DGGE (1.27; 95% CI: 1.01-1.62), PCR-RFLP (1.88; 95% CI: 1.42-2.49) and PCR-seq (1.34; 95% CI: 1.14-1.58) showed statistically significant impact on survival of NSCLC patients. In conclusion, this meta-analysis suggests that K-RAS mutations are associated with a worse overall survival in patients with NSCLC, especially in patients with adenocarcinoma and early stage.

People with a family history of colorectal cancer (CRC) are at increased risk of developing the disease. Information on the screening practices of this segment of the population is scarce.

Cytochrome P450 2E1 (CYP2E1) is a natural enzyme involved in the metabolic activation of many carcinogens, and the functional polymorphisms in the CYP2E1 gene might have impacts on colorectal cancer risk. Many studies were published to assess the associations of CYP2E1 rs2031920 and rs3813867 polymorphisms with colorectal cancer risk, but no consistent findings were reported. A systemic review and meta-analysis of eligible studies was performed to comprehensively assess the associations above. Odds ratios (ORs) with 95 % confidence interval (95 % CIs) were used to assess the strength of the associations. Seventeen studies from 15 publications with 17,082 individuals were finally included into this meta-analysis. Meta-analysis of the 13 studies on CYP2E1 rs2031920 polymorphism showed that there was a significant association between CYP2E1 rs2031920 polymorphism and colorectal cancer risk under two genetic models (c2 versus c1: OR = 1.19, 95 % CI 1.03-1.37, P = 0.022; c2c2/c2c1 versus c1c1: OR = 1.16, 95 % CI 1.00-1.35, P = 0.046). Meta-analysis of those four case-control studies on CYP2E1 rs3813867 polymorphism showed that there was no significant association between CYP2E1 rs3813867 polymorphism and colorectal cancer risk under all contrast models (c2 versus c1: OR = 0.96, 95 % CI 0.80-1.16, P = 0.672; c2c2 versus c1c1: OR = 1.26, 95 % CI 0.43-3.67, P = 0.672; c2c2/c1c2 versus c1c1: OR = 0.95, 95 % CI 0.78-1.16, P = 0.114; and c2c2 versus c1c2/c1c1: OR = 1.17, 95 % CI 0.41-3.36, P = 0.775). Therefore, the findings from this meta-analysis suggest that CYP2E1 rs2031920 polymorphism is associated with colorectal cancer risk, but CYP2E1 rs3813867 polymorphism is not associated with colorectal cancer risk. In addition, more well-designed studies with large sample size are needed to provide a more precise evaluation on the associations above.

Leptomeningeal carcinomatosis (MC) represents an uncommon, but devasting manifestation of metastatic breast cancer. This is the first systematic review/pooled analysis to synthesize all available data evaluating the efficacy and safety of intrathecal (IT) administration of trastuzumab for the treatment of MC in HER2-positive breast cancer patients. This study was performed in accordance with the PRISMA guidelines. A total of 13 articles (17 patients) were eligible. The mean age of patients at IT trastuzumab administration was 48.2 years (SD 8.4, range 38-66). The mean total dose was 399.8 mg (SD 325.4, range 35-1,110 mg). IT trastuzumab alone or as part of combination therapies seemed to be safe; no serious adverse events were reported in 88.2 % of cases. In 68.8 % of cases, a significant clinical improvement was observed, while stabilization or progression of the disease was noticed in 31.2 % of cases. Cerebrospinal fluid (CSF) response was noted in 66.7 % of cases. The median overall survival was 13.5 months, whereas the median central nervous system progression-free survival (CNS-PFS) was 7.5 months. In 23.5 % of cases, IT trastuzumab was administered beyond CNS progression with a response noticed in 75 % of cases and a CNS-PFS of 9.4 months. The cumulative dose of IT trastuzumab given was 1,040 mg (SD 697.9, median 1,215, range 55-1,675). The protective effect of prior radio- or neurosurgery upon CNS-PFS was sizeable but did not reach formal statistical significance (HR 0.28, 95 % CI 0.06-1.37). Clinical improvement (HR 0.14, 95 % CI 0.02-0.91) and CSF response (HR 0.09, 95 % CI 0.01-0.89) were associated with longer CNS-PFS. IT trastuzumab administration seems to represent a safe and in some cases effective option for the treatment of HER2-positive breast cancer patients with leptomeningeal involvement. However, clinical trials are urgently needed to establish the definite role of IT trastuzumab in HER2-positive metastatic breast cancer patients with MC.

The association between the deficiency in mismatch repair (MMR) genes and prognosis in women with endometrial cancer is unclear. Here we report a systematic review and meta-analysis exploring this association.

To describe the frequency of MLH1 promoter methylation in colorectal cancer (CRC); to explore the associations between MLH1 promoter methylation and clinicopathological and molecular factors using a systematic review and meta-analysis.

A summary of the evidence pertaining to the association between methylenetetrahydrofolate reductase (MTHFR) C677T and overall survival in pediatric acute lymphoblastic leukemia (ALL) is not currently available. We thus reviewed the literature on the association between MTFHR C677T and overall survival in pediatric ALL. We searched PubMed/MEDLINE, Scopus and ISI Web of Knowledge literature databases without language restrictions to identify observational studies among children diagnosed between ages 0 and 19 years that assessed MTHFR 677 polymorphisms in relation to ALL survival. We identified six studies comprising 909 pediatric patients with ALL. The magnitude of relative risk (RR) for pediatric ALL mortality varied by genotype comparison and study population, ranging from RR = 0.84 (95% confidence limits [CL]: 0.24, 3.0) for a TT vs. CT/CC comparison to RR = 7.0 (95% CL: 0.98, 49) for a TT vs. CC comparison. The current evidence suggests that individuals with MTHFR 677 variants (i.e. at least one T allele) may have a higher relative risk of pediatric ALL mortality, with greater statistical support for MTHFR 677TT. With more detailed supporting evidence, MTHFR 677 genotyping at diagnosis could provide an option for individualizing therapy and further reducing pediatric ALL mortality in certain populations.

Lung cancer is the leading cause of cancer deaths worldwide, and has one of the lowest survival rates of any solid tumor. In recent years, several attempts have been conducted to improve an early or accelerated diagnosis due to better overall prognosis after therapy. The aim of this study was evaluating the use of genetic markers for diagnosis of lung cancer. This study was conducted in accordance to Transparent Reporting of Systematic Reviews and Meta-Analyses. Three Internet sources were used to search: MEDLINE-PubMed, EMBASE, and LILACS. The databases were searched for studies conducted in the period up to and including May 10, 2011. The following inclusion criteria were applied: lung cancer studies, and the use of genetic markers for diagnosis. Studies using animal models, review articles, meta-analyses, abstracts, conference proceedings, editorials/letters, case reports, incorrect study population, inadequate data, and cytology was not obtained, were excluded. A total of 1,901 abstracts/citations were identified for preliminary review. From 24 final selected studies, 17 referred to chromosomal markers diagnosis, eight to genes as marker, and one to both subjects. Fluorescence in situ hybridization (FISH) was applied in all studies. Despite the limitations of this study, application of genetic markers to lung cancer diagnosis seems to have prognosis value irrespective of detection methodology used. FISH was the main technique applied to diagnose genetics alterations and revealed a high specificity, although some authors reported low sensitivity.

The aim of this systematic review is to summarize the current knowledge about the etiology and pathogenesis of borderline tumors ovarian cancer with special emphasis on the role of endocrine treatments and reproductive factors to establish a foundation for future studies.

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.

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).

The epidermal growth factor receptor (EGFR) gene copy number (GCN) has been previously demonstrated to correlate with the clinical outcome of colorectal cancer (CRC) treated with anti-EGFR monoclonal antibodies (mAbs), although it remains controversial. We conducted a systematic review and meta-analysis to assess EGFR GCN as a potential biomarker of survival for patients with advanced CRC receiving treatment with anti-EGFR mAbs.

Budd-Chiari syndrome (BCS) can be incidentally complicated by hepatocellular carcinoma (HCC), thereby decreasing the survival of these patients. Our study aims to systematically review the prevalence and risk factors of HCC in BCS patients.

CD133 has recently been reported as a marker of cancer stem-like cells in colorectal cancer (CRC). However, its predictive value in CRC still remains controversial. In this study, we aimed to evaluate the association between the expression of CD133 and clinicopathological features and the outcome of CRC patients by performing a meta-analysis.

Emerging evidence showed that common functional -31G>C polymorphism (rs9904341 G>C) in the promoter region of the survivin gene is involved in the regulation of survivin expression, thus increasing an individual's susceptibility to gastrointestinal tract (GIT) cancer; but individually published results are inconclusive. The aim of this systematic review and meta-analysis was to derive a more precise estimation of the association between survivin -31G>C polymorphism and GIT cancer risk.

The metabolism of folate involves a complex network of polymorphic enzymes that may explain a proportion of the risk associated with colorectal neoplasia. Over 60 observational studies primarily in non-Hispanic White populations have been conducted on selected genetic variants in specific genes, MTHFR, MTR, MTRR, CBS, TCNII, RFC, GCPII, SHMT, TYMS, and MTHFD1, including five meta-analyses on MTHFR 677C>T (rs1801133) and MTHFR 1298C>T (rs1801131); two meta-analyses on MTR-2756A>C (rs1805087); and one for MTRR 66A>G (rs1801394).

Preterm Birth (PTB) is a major cause of neonatal mortality and morbidity. Women with Polycystic Ovary Syndrome (PCOS) are at high risk of PTB. There is a need for research studies to investigate the mechanisms linking PCOS and PTB, to facilitate screening, and develop novel preventative strategies.

The prognostic significance of p16 promoter hypermethylation in patients with non-small cell lung cancer (NSCLC) is still controversial. This analysis presents pooled estimates of the association to better elucidate whether p16 methylation has a prognostic role in NSCLC.

To evaluate the prevalence and spectrum of BRCA mutations among ovarian carcinoma patients of different races and ethnicity with special reference to Asia.

Metastatic colorectal cancer (mCRC) imposes a substantial health burden on individual patients and society. Furthermore, rising costs in oncology cause a growing concern about reimbursement for innovations in this sector. The promise of pharmacogenomic profiling and related stratified therapies in mCRC is to improve treatment efficacy and potentially save costs. Among other examples, the commonly used epidermal growth factor receptor (EGFR) antibodies cetuximab and panitumumab are only effective in patients with kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type cancers. Hence, the adaptation of predictive biomarker testing might be a valid strategy for healthcare systems worldwide.