Nijmegen Breakage Syndrome protein 1 (NBS1) is one of the most important DNA repair proteins playing important roles in maintaining the genomic stability of NDA. Previous studies regarding the association between NBS1 8360G>C (Glu185Gln) polymorphism and lung cancer reported conflicting results. To derive a more precise estimation of this association, a systemic review and meta-analysis was performed. We performed a meta-analysis using eligible case-control studies to summarize the data on the association between the NBS1 Glu185Gln polymorphism and lung cancer risk. Odds ratios (ORs) with corresponding 95 % confidence intervals (95 %CIs) were pooled to assess the association between NBS1 Glu185Gln polymorphism and lung cancer risk. Six case-control studies with a total of 2,348 lung cancer cases and 2,401 controls without canner were included into the meta-analysis. Overall, there was an association between NBS1 Glu185Gln polymorphism and lung cancer risk under the dominant comparison model (fixed-effects OR GluGln/GlnGln vs. GluGlu = 1.21, 95 % CI 1.07-1.37, P = 0.002, I (2) = 8.1 %). Subgroup analysis by race suggested a significant association between NBS1 Glu185Gln polymorphism and lung cancer risk in Asians (fixed-effects OR GluGlnGlnGln vs. GluGlu = 1.22, 95 % CI 1.06-1.41, P = 0.005) but not in Caucasians (fixed-effects OR GluGlnGlnGln vs. GluGlu = 1.17, 95 % CI 0.91-1.50, P = 0.220). This meta-analysis supports that there is an association between NBS1 Glu185Gln polymorphism and lung cancer risk. More studies are needed to further verify this association.

This study synthesized scientific literature that applies genetic or genomic approaches to breastmilk. A literature search of PubMed was conducted in March 2012 using the key words "breast milk," "lactation," "genetic," "gene expression," and "epigenetic." Additional articles were identified/selected for evaluation with MeSH term searches, and a review of article reference lists was obtained from the search. The initial 657 abstracts retrieved from the literature search were reviewed, and 16 studies were selected for evaluation. Studies that examined the transmission of viruses/bacteria into breastmilk and/or measured concentration of specific proteins without examination of genetic material from milk were excluded. Data related to subjects, tissue, purpose, setting, gene/protein, approach (candidate versus genome-wide), platform, statistical analysis, and results were extracted. Gene expression and epigenetic/epigenomic study designs have been successfully implemented using breastmilk. A major weakness of both gene expression studies and epigenetic studies that examine breastmilk is the omission of maternal information known to influence milk composition. This review article is the first to synthesize evidence related to the application of breastmilk to evaluate RNA and epigenetic modifications. Additional research is needed that applies epigenetic analyses to human breastmilk samples. Findings from this review can be used for future research designs that use breastmilk for genetic analyses.

Thyroid cancer is the most common endocrine neoplasm accounting for approximately 1,7% of total cancer diagnoses. The gold standard for evaluation of thyroid nodules is cytology from fine needle aspiration. In 30% of biopsies there is no conclusive diagnosis and patients undergo a diagnostic hemithyroidectomy. Somatic mutations occur frequently in thyroid cancer, the value of testing FNA biopsies on different mutation is analyzed, it improves accuracy, but their sensitivity is low. Another class of molecules with potential diagnostic value are miRNAs (miRNA, miR). MiRNAs function as gene regulators thereby controlling many cellular processes including cell growth, differentiation, proliferation, and apoptosis. Several studies have analyzed the expression of miRNAs in thyroid cancer, either by performing microarray analyses or validating a set of miRNAs. Recent reports focused on the diagnostic value of miRNAs in indeterminate FNA biopsies. In this systematic review we will provide an overview of all miRNAs found to be up- or downregulated in the different types of thyroid carcinomas, give an overview of the value of validated sets of microRNAs or single microRNAs in distinguishing malignant from benign lesions and conclude with a clinical view on future study strategies.

The aim of this study was to summarize the global predicting role of hormone receptors for survival in ovarian cancer.

The association between MTHFR Ala222Val polymorphism and breast cancer (BC) risk are inconclusive. To derive a more precise estimation of the relationship, a systematic review and meta-analysis was performed.

Surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF-MS) has been approved for identifying biomarkers and diagnosing many diseases such as lymphomas. It is arguable whether the SELDI technique has its value of diagnostic accuracy for lymphomas. The purpose of our study is to determine the diagnostic accuracy of SELDI-TOF-MS for diagnosing lymphomas. The Cochrane Central Register of Controlled Trials, MEDLINE, Pub Med, EMBASE, the Chinese Biomedical Literature Database, the China Academic Journals Full-text Database, and the Chinese Scientific Journals Database were searched systematically for potential studies. Reference lists of included studies and review articles were also reviewed. All studies that reported data on patients with a confirmed diagnosis of lymphomas and that compared the measurement of SELDI-TOF-MS with pathology standard were considered for inclusion. Eleven studies were included in the systematic review. The ranges of the diagnostic value of SELDI-TOF-MS for lymphoma were as follows: sensitivity (SEN) was 0.69-0.96; specificity (SPE) was 0.70-1.00; positive likelihood ratio (PLR) was 2.99-96.09; negative likelihood ratio (NLR) was 0.04-0.35; and diagnostic odds ratio (DOR) was 18.13-1250.71, respectively. Further, we analysed serum samples as a subgroup, and the pooled endpoints were as follows: pooled SEN was 0.89 (0.85-0.91); pooled SPE was 0.91 (0.88-0.93); pooled PLR was 12.35 (5.36-28.44); pooled NLR was 0.13 (0.09-0.20); and pooled DOR was 101.04 (39.57-258.04), respectively. SELDI-TOF-MS showed high accuracy in identifying lymphoma and could be a useful screening tool for diagnosing lymphoma patients.

To explore the association between polymorphisms in the DNA repair gene, xeroderma pigmentosum group D (XPD), and development of hepatocellular carcinoma (HCC) in the Chinese population by performing a systematic review of the previously published clinical data.

Polycystic ovary syndrome (PCOS) is characterized by ovulatory dysfunction and hyperandrogenism. Its etiopathology is not well understood but genetic factors seem to have a role. Polymorphism of the androgen receptor (AR) gene has been associated with different androgen pattern diseases.

Mutations of the tumor suppressor gene TP53 are the most significant events in several human cancers. Few studies have analyzed the frequency of TP53 alterations in squamous cell carcinoma and adenocarcinoma of the cervix with controversial results. This study provides a detailed analysis of TP53 mutation spectra in cervical squamous cell carcinoma and adenocarcinoma from different geographical regions.

The diagnosis of malignant mesothelioma (MM) remains a clinical challenge and the fluorescence in situ hybridization (FISH) assay has been reported to be one promising tool. The present meta-analysis aimed to establish the overall diagnostic accuracy of FISH for diagnosing MM. After a systematic review of English language studies, the sensitivity, specificity and other measures of accuracy of FISH in the diagnosis of MM were pooled using random-effects models. Summary receiver operating characteristic curves were applied to summarize overall test performance. Nine studies met our inclusion criteria, the pooled sensitivity and specificity for FISH for diagnosing MM being 0.72 (95% CI 0.67-0.76) and 1.00 (95% CI 0.98-1.00), respectively. The positive likelihood ratio was 34.5 (95% CI 14.5-82.10), the negative likelihood ratio was 0.24 (95% CI 0.16-0.36), and the diagnostic odds ratio was 204.9 (95% CI 76.8-546.6), the area under the curve being 0.99. Our data suggest that the FISH assay is likely to be a useful diagnostic tool for confirming MM. However, considering the limited studies and patients included, further large scale studies are needed to confirm these findings.

The traditional staging system is inadequate to identify those patients with stage II colorectal cancer (CRC) at high risk of recurrence or with stage III CRC at low risk. A number of gene expression signatures to predict CRC prognosis have been proposed, but none is routinely used in the clinic. The aim of this work was to assess the prediction ability and potential clinical usefulness of these signatures in a series of independent datasets.

RAS association domain family protein 1a (RASSF1A) is a putative tumor suppressor gene located on 3p21, has been regarded playing important roles in the regulation of different types of human tumors. Previous reports demonstrated that the frequency of RASSF1A methylation was significantly higher in patients group compared with controls, but the relationship between RASSF1A promoter methylation and pathological features or the tumor grade of bladder cancer remains controversial. Therefore, A meta-analysis of published studies investigating the effects of RASSF1A methylation status in bladder cancer occurrence and association with both pTNM (p, pathologic stage; T, tumor size; N, node status; M, metastatic status) and tumor grade in bladder cancer was performed in the study. A total of 10 eligible studies involving 543 cases and 217 controls were included in the pooled analyses. Under the fixed-effects model, the OR of RASSF1A methylation in bladder cancer patients, compared to non-cancer controls, was 8. 40 with 95%CI=4. 96-14. 23. The pooled OR with the random-effects model of pTNM and tumor grade in RASSF1A methylated patients, compared to unmethylated patients, was 0. 75 (95%CI=0. 28-1. 99) and 0. 39 (95%CI=0. 14-1. 09). This study showed that RASSF1A methylation appears to be an independent prognostic factor for bladder cancer. The present findings also require confirmation through adequately designed prospective studies.

The x-ray cross complementing group 1 gene (XRCC1) is crucial to proper repair of DNA damage such as single-strand DNA breaks. A non-synonymous polymorphism in XRCC1, 399 G → A, has been shown to reduce effectiveness of such DNA repair and has been associated with the risk of certain cancers. The known risk for glioma from high dose ionizing radiation makes associations between this polymorphism and glioma of particular interest.

The main objective of this study was to perform a systematic review and meta-analysis on the risk of developing malignant paraganglioma (PGL) in SDHB-mutation and SDHD-mutation carriers. PubMed, EMBASE, Web of Science, COCHRANE and Academic Search Premier (2000-August 2011) and references of key articles were searched to identify potentially relevant studies. The main outcomes were the pooled incidence and prevalence of malignant PGL in SDHB-mutation and SDHD-mutation carriers. A meta-analysis was performed with an exact likelihood approach using a logistic regression with a random effect at the study level. Twelve studies were included. The pooled incidence of malignant PGL in populations comprising both asymptomatic mutation carriers and mutation carriers with manifest non-malignant PGL was 17% (95% CI 10 to 28) for SDHB-mutation carriers and 8% (95% CI 2 to 26) for SDHD-mutation carriers. The pooled risk in prevalence studies was 13% (95% CI 4 to 34) and 4% (95% CI 2 to 7), respectively. In studies comprising only mutation carriers with manifest disease, the pooled prevalence was 23% (95% CI 16 to 33) for SDHB-mutation and 3% (95% CI 1 to 10) for SDHD-mutation carriers. Incidence and prevalence of malignant PGL are higher in SDHB-mutation than in SDHD-mutation carriers, but lower in SDHB-mutation carriers than hitherto appreciated.

This systematic review investigated the inheritance of the classical chronic myeloproliferative neoplasms (MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) and chronic myelogenous leukemia (CML). Sixty-one articles were included and provided 135 families with a total of 341 participants distributed to various subtypes of MPN: 50% PV, 23% ET, 14% PMF, 10% CML and 3% non-MPN hematological disorder. Women developed the disease earlier than men (43.1 years vs 47.3 years; p = 0.074), while the general average age of onset was 46 years, notably younger than sporadic cases. The clinical phenotype of the families showed a homogenous (67%) and a heterogeneous (33%) pattern, with the majority being PV-PV pairs (36%) and PV-PMF pairs (17%), respectively. This observation suggests that the susceptibility gene (or genes) is not restricted to one subtype supporting the hypothesis of a mutation in an early multipotent stem cell. Furthermore, a major subgroup of families provided evidence of an autosomal dominant (AD) inheritance with reduced penetrance. This study suggests that the origin of MPNs may occur in at least three different settings: (i) a sporadic, (ii) genetic heterogeneity with polygenetic and environmental impact and (iii) a familial phenotype following an AD inheritance.

Methotrexate (MTX) is an important component of therapy used to treat childhood acute lymphoblastic leukemia (ALL). Two single-nucleotide polymorphisms (SNPs) in the methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C, affect MTHFR activity. A large body of studies has investigated the potential role of MTHFR SNPs in MTX toxicity in pediatric ALL. However, the results are controversial. In this review and meta-analysis, we critically evaluate the relationship between the C677T and A1298C polymorphisms of MTHFR and MTX toxicity in pediatric ALL. The majority of published reports do not find associations between MTHFR polymorphisms and toxicity in pediatric ALL. When associations are reported, often the results are contradictory to each other. The meta-analysis confirms a lack of association. In conclusion, MTHFR, C677T and A1298C polymorphisms do not seem to be good markers of MTX-related toxicity in pediatric ALL.

A meta-analysis was performed to compare KRAS gene mutations in colorectal cancer tissue samples with primary and metastatic colorectal cancers. A total of 19 publications with 986 paired primary and distant metastases and 171 paired primary and lymph node metastases showed that KRAS genotype was highly concordant in primary and distant metastatic tumors, indicating that either type of tumor tissue could be useful as a source to detect KRAS mutations for selection of anti-EGFR therapy. However, lymph-node-metastatic tumors might not be suitable for diagnostic analysis of KRAS mutations due to an obvious discordant rate between primary and lymph-node-metastatic tumors.

To perform a meta-analysis investigating the association of MTHFR C677T polymorphism and susceptibility of cervical cancer. All case-control studies published in English and Chinese with estimates of the relationship between MTHFR C677T polymorphism and risk of cervical cancer were analyzed using odds ratio (OR) with 95 % confidence interval (CI). A total of 10 studies (2,023 cases and 2,570 controls) were included in the meta-analysis. No significant association was observed between T allele and C allele (OR = 0.90; 95 %CI = 0.70-1.17; P = 0.43), and for genotype TT versus CC (OR = 1.09; 95 %CI = 0.74-1.61; P = 0.67), CT versus CC (OR = 0.95; 95 %CI = 0.75-1.20; P = 0.65), CT + TT versus CC (OR = 0.91; 95 %CI = 0.66-1.24; P = 0.55). The current meta-analysis results suggest that the MTHFR C677T polymorphism may not be associated with cervical cancer.

Cervical cancer develops through progression from normal cervical epithelium through squamous intraepithelial lesions (SIL) to invasive cancer. Cervical cancer is associated with oncogenic human papillomavirus (HPV). The HPV E6 oncoprotein binds to the tumor suppressor gene product p53, promoting its degradation; the Arg allele of p53 Arg72Pro polymorphism binds more ardently with HPV E6 than the Pro variant. Here we evaluate the role of p53 Arg72Pro polymorphism and HPV status on the initiation, progression, and development of cervical cancer. A systematic review and meta-analysis were conducted. Events of interest were the initiation of neoplasia (SIL vs. normal), progression to invasive cancer (cervical cancer vs. SIL), and risk of invasive cancer (cervical cancer vs. normal) by HPV status. OR were extracted from individual studies and pooled using generic inverse variance and random effects modeling. Forty-nine studies were included. In individuals showing HPV positivity, there was a significantly higher odds of progression from SIL to cervical cancer with the p53 Arg allele [OR 1.37; 95% confidence intervals (CI), 1.15-1.62; P < 0.001]. This association was not seen in HPV-negative individuals. p53 Arg72Pro was not associated with the risk of cervical cancer or initiation of SIL in either HPV-positive or HPV-negative patient subsets. The Arg variant of p53 Arg72Pro is associated with progression of SIL to cervical cancer only in the presence of HPV positivity. There were no associations of this variant with overall risk or initiation of cancer in either HPV-positive or HPV-negative patients. Clin Cancer Res; 18(23); 6407-15.

There is increasing evidence for the role of altered metabolism in the pathogenesis of renal cancer.