Polo-like kinase 1 (PLK1) is a potential prognostic marker in colorectal cancer (CRC). Nevertheless, the clinicopathological and prognostic roles of PLK1 in CRC are still undefined. Therefore, we performed a meta-analysis to investigate the clinicopathological and prognostic relevance of PLK1 expression in CRC patients.

Polycystic ovary syndrome (PCOS) is a highly prevalent disease in young women that also features increased insulin resistance. Genetic factors have a strong relationship with the etiology of PCOS. We assessed whether carrying THADA rs13429458 is associated with the development of PCOS by meta-analysis and whether the association is influenced by ethnicity. Articles were searched using PubMed, EMBASE, Cochrane Library, Korean scientific database, and Chinese and Indian medical databases to identify all eligible studies for evaluating the association of THADA rs13429458 and PCOS risk. The association was assessed in five genetic random effects models including the allelic (AG), recessive (RG), dominant (DG), homozygous (HMG), and heterozygous (HTG) genetic models. Subgroup analyses stratified by ethnicity (Asians and non-Asians) were assessed. Nine articles were selected and 1 association analysis of Korea PCOS study met Hardy-Weinberg equilibrium criteria. A set of 38 224 PCOS women and 120 173 healthy women were included. The AG and RG showed heterogeneity in the overall and Asian subjects, but the other genetic model did not exhibit heterogeneity in all subjects. AG, RG, DG, and HMG, but not HTG, exhibited publication bias in total subjects but there was no publication bias in all genetic models among Asians and non-Asians. The overall effect of THADA_rs13429458 on PCOS risk showed significant positive associations in pooling 10 studies. In sub-group analysis only Asians, but not non-Asians, had a positive association (AG: OR=1.24, p=0.001; RG: OR=1.32, p=0.002; DG: OR, 1.70, p<0.00001; HMG: OR, 1.71, p=0.002; HTG: OR=1.34, p=0,006). In conclusions, young Asian women with the minor allele (C) for THADA rs13429458 were at increased risk of PCOS.

Understanding the prevalence and biology of BRAF gene can improve the treatment methods of cancerous patients. This study aims to estimate the prevalence of BRAF gene mutation in samples of primary and metastatic colorectal cancer using meta-analysis method.

Not all patients respond well to cancer chemotherapy. One of the most important factors contributing to treatment response (efficacy and toxicity) is genetic determinant. The current systematic review aims to provide current status of the information on the genetic contribution of genes encoding drug transport proteins and drug metabolizing enzyme, cytochrome P450 (CYP), and relationship with clinical outcomes of cancer chemotherapy.

Medications to reduce risk of breast cancer are effective for women at increased risk but also cause adverse effects.

Studies investigating the relationships between the polymorphisms in the X-ray repair cross complementing 1 (XRCC1) gene and the susceptibility of hepatocellular carcinoma (HCC) remained controversial, therefore, we assessed this associations by metaanalysis and trial sequential analysis (TSA). PubMed, Embase, Google Scholar, Chinese National Knowledge Infrastructure and Baidu Scholar were comprehensively screened to retrieve relevant studies up to May 20, 2019. A total of 32 studies was included. Significant associations were discovered in the overall and subgroup analysis in these three polymorphisms. Interestingly, the decreased risk of HCC was detected in the Indians for the rs24587 polymorphism. TSA indicated the required information size for the rs25487 polymorphism were reached, but for the rs25489 and rs1799782 polymorphisms, more well-designed trials were required. Sensitivity analysis implied our results were stable; no publication bias was observed in the rs25487 and rs1799782 polymorphisms. The bioinformatic analysis indicate that the rs1799782 polymorphism is probably damaging and has an influence on the XRCC1 protein function. Our study indicated that the XRCC1 rs25487 was a risk factor for the susceptibility of HCC, which was verified by the TSA. In addition, the rs25489 and rs1799782 polymorphisms were associated with increased risk of HCC. In the subgroup analysis, increased risks were detected in some subgroups (in accordance with Hardy-Weinberg equilibrium, Chinese groups, Mongoloid subgroup, polymerase chain reaction-restriction fragment length polymorphisms and more than 300 subgroups), moreover, decreased HCC risk of the rs25487 polymorphism was firstly observed, which required further studies to verify.

The relationship between first-degree family history of female breast cancer and prostate cancer risk in the general population remains unclear. We performed a meta-analysis to determine the association between first-degree family history of female breast cancer and prostate cancer risk.

The first study establishing exposure to ionizing radiations (IRs) as a risk factor for differentiated thyroid cancer (DTC) was published 70 years ago. Given that radiation exposure causes direct DNA damage, genetic alterations in the different DNA repair mechanisms are assumed to play an important role in long-term IR-induced DNA damage prevention. Individual variations in DNA repair capacity may cause different reactions to damage made by IR exposure. The aim of this review is to recapitulate current knowledge about constitutional genetic polymorphisms found to be significantly associated with DTC occurring after IR exposure. Studies were screened online using electronic databases - only fully available articles, and studies performed among irradiated population or taking radiation exposure as adjustment factors and showing significant results are included. Nine articles were identified. Ten variants in/near to genes in six biological pathways, namely thyroid activity regulations, generic transcription, RET signaling, ATM signaling and DNA repair pathways were found to be associated with radiation-related DTC in these studies. Only seven variants were found to be in interaction with IR exposure in DTC risk. Most of these variants are also associated to sporadic DTC and are not specific to IR-related DTC. In the published studies, no data on children treated with radiotherapy is described. In conclusion, more studies carried out on larger cohorts or on case-control studies with well-documented individual radiation dose estimations are needed to get a comprehensive picture of genetic susceptibility factors involved in radiation-related DTC.

After The Cancer Genome Atlas (TCGA) findings, four novel prognostic groups may direct the management of endometrial cancer (EC): POLE-mutated/ultramutated (POLEmt), microsatellite-instable/hypermutated (MSI), copy-number-low/p53-wild-type (p53wt), and copy-number-high/p53-mutated (p53mt). However, data about prognosis in each group are different across the studies, and definitive pooled estimates are lacking after validation series. Such data may be crucial in directing clinical study design and establishing the optimal tailored management of patients.

MiR-221, acting as onco-miR or oncosuppressor-miR, plays an important role in tumor progression; however, the prognostic value of miR-221 in human carcinomas is controversial and inconclusive. The objective of our study was to conducted a systematic review and meta-analysis of miR-221 in various types of human cancers.

Cancer is a genetic and epigenetic disease that involves inactivation of tumor suppressor genes and activation of proto-oncogenes. All-trans retinoic acid (ATRA) is an isomer of retinoic acid involved in the onset of differentiation and apoptosis of a number of normal and cancer cells, functioning as an anti-cancer agent in several neoplasms. Ectopic changes in the expression of certain microRNAs (miRNAs) occur in response to ATRA, leading to phenotypic alterations in neoplastic cell lines. Moreover, the modulation of miRNA patterns upon ATRA-treatment may represent an effective chemopreventive and anti-cancer therapy strategy. The present systematic review was performed to provide an overview of the modulation of ATRA-induced miRNA expression in different types of neoplastic cells and identify the efficacy of intervention factors (i.e., concentration and duration of treatment) and how they influence expression profiles of oncogenesis-targeting miRNAs.

Background: Gene panels are routinely used to assess predisposition to hereditary cancers by simultaneously testing multiple susceptibility genes and/or variants. More recently, genetic panels have been implemented as part of solid tumor malignancy testing assessing somatic alterations. One example is targeted variant panels for thyroid nodules that are not conclusively malignant or benign upon fine-needle aspiration (FNA). We systematically reviewed published studies from 2009 to 2018 that contained genetic data from preoperative FNA specimens on cytologically indeterminate thyroid nodules (ITNs) that subsequently underwent surgical resection. Pooled prevalence estimates per gene and variant, along with their respective positive predictive values (PPVs) for malignancy, were calculated. Summary: Our systematic search identified 540 studies that were supplemented by 18 studies from bibliographies or personal files. Sixty-one studies met all inclusion criteria and included >4600 ITNs. Overall, 26% of nodules contained at least 1 variant or fusion. However, half of them did not include details on the specific gene, variant, and/or complete fusion pair reported for inclusion toward PPV calculations. The PPVs of genomic alterations reported at least 10 times were limited to BRAFV600E (98%, 95% confidence interval [CI 96-99%]), PAX8/PPARG (55% [CI 34-78%]), HRASQ61R (45% [CI 22-72%]), BRAFK601E (42% [CI 19-68%]), and NRASQ61R (38% [CI 23-55%]). Excluding BRAFV600E, the pooled PPV for all other specified variants and fusions was 47%. Multiple variants within the same nodule were identified in ∼1% of ITN and carried a cumulative PPV of 77%. Conclusions: The chance that a genomic alteration predicts malignancy depends on the individual variant or fusion detected. Only five alterations were reported at least 10 times; BRAFV600E had a PPV of 98%, while the remaining four had individual PPVs ranging from 38% to 55%. The small sample size of most variants and fusion pairs found among ITNs, however, limits confidence in their individual PPV point estimates. Better specific reporting of genomic alterations with cytological category, histological subtype, and cancer staging would facilitate better understanding of cancer prediction, and the independent contribution of the genomic profile to prognosis.

L1 cell adhesion molecule (L1CAM) is a glycoprotein involved in cancer development and is associated with metastases and poor prognosis. Cellular processing of L1CAM results in expression of either full-length or cleaved forms of the protein. The different forms of L1CAM may localize at the plasma membrane as a transmembrane protein, or in the intra- or extracellular environment as cleaved or exosomal forms. Here, we systematically analyze available literature that directly relates to L1CAM domains and associated signaling pathways in cancer. Specifically, we chart its domain-specific functions in relation to cancer progression, and outline pre-clinical assays used to assess L1CAM. It is found that full-length L1CAM has both intracellular and extracellular targets, including interactions with integrins, and linkage with ezrin. Cellular processing leading to proteolytic cleavage and/or exosome formation results in extracellular soluble forms of L1CAM that may act through similar mechanisms as compared to full-length L1CAM, such as integrin-dependent signals, but also through distinct mechanisms. We provide an algorithm to guide a step-wise analysis on L1CAM in clinical samples, to promote interpretation of domain-specific expression. This systematic review infers that L1CAM has an important role in cancer progression that can be attributed to domain-specific forms. Most studies focus on the full-length plasma membrane L1CAM, yet knowledge on the domain-specific forms is a prerequisite for selective targeting treatment.

Glutathione S-transferases (GSTs) contain a series of critical enzymes regulating proliferation or apoptosis in the tumor microenvironment. Data from publications about the correlation between Glutathione S-transferase Pi 1 (GSTP1) gene 313 A/G (rs1695) polymorphism and bladder caner (BCa) remained controversial. To explore the exact correlation between this polymorphism and the development of BCa, we carried out this study.

RASSF2 is a tumor suppressor gene closely related to gastric cancer. This meta-analysis was designed to assess the quality in the previous studies and establish the value of RASSF2 methylation in the prediction and prognosis of gastric cancer. The eligible literatures with publication deadline of May 3, 2019 were collected from PubMed, EMBASE, CNKI, Wanfang, and CNVIP databases. The correlation between RASSF2 methylation level and gastric cancer was estimated by odds ratio and 95% confidence interval (OR and 95% CI) values. A total of eight articles were included in the study. A total of 517 gastric cancer tissue samples and 517 adjacent nontumor tissue samples were included. The results of the analysis showed that RASSF2 had a significantly higher level of methylation in gastric cancer (OR = 17.56, 95% CI = 7.11-43.35, p-value = 0.009). Meanwhile, we tested whether there was association of RASSF2 methylation with tumor metastasis, and we also analyzed whether there was a gender difference in RASSF2 methylation. However, our results showed no statistical significance of the two aforementioned tests (p > 0.1). Our study suggested that RASSF2 methylation could predict the risk of gastric cancer. However, it might not be feasible for the prediction of tumor metastasis.

A series of studies have investigated the vital role of microRNA-181 (miR-181) in the initiation and development of colorectal cancer (CRC), and demonstrated that it might be associated with the prognosis of CRC. However, inconsistent findings have hindered its clinical application.

One-step nucleic acid amplification (OSNA) is used to intraoperatively detect sentinel lymph node metastases in breast cancer. OSNA has also been proposed in endometrial cancer, but evidence in this regard is unclear to define the diagnostic accuracy of OSNA in detecting lymph node metastases in endometrial cancer. A systematic review and meta-analysis was performed by searching 8 electronic databases from their inception to March 2019 for studies testing the diagnostic accuracy of OSNA in detecting sentinel lymph node metastasis in endometrial cancer. Pathologic ultrastaging was the reference standard. Sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR-), diagnostic odds ratio (DOR) and area under the curve (AUC) on SROC curve were calculated. Four studies with 237 patients and 691 lymph nodes were included. OSNA showed sensitivity = 0.88, specificity = 0.93, LR + =17.95, LR- = 0.15, DOR = 191.23 and high diagnostic accuracy (AUC = 0.959). OSNA appears as a highly accurate tool for intraoperative assessment of sentinel lymph node in endometrial cancer.

Small cell lung cancer (SCLC) is a highly invasive and lethal neuroendocrine tumor. Antiangiogenic drugs have been reported in the treatment of SCLC. We aimed to provide a comprehensive evaluation of the impact of angiogenic inhibitors on SCLC survival using network meta-analysis.

To investigate the prevalence of EML4-ALK variants in non-small-cell lung cancer (NSCLC) patients. Materials & methods: Database of Pubmed, Embase, Medline and Cochrane Library were searched systematically to April 2018. Results: A total of 39 articles including 1903 NSCLC patients with ALK positive were recruited. The overall pooled prevalence for EML4-ALK variant 1 to 3 was 81.84% (95% CI: 76.68-86.99%), ranging from 86.64% tested by RT-PCR to 70.85% tested by other methods (p = 0.00). Subgroup analysis showed that the pooled prevalences of variant 1, 2 and 3 were 40.38% (95% CI: 34.83-45.93%), 6.59% (95% CI: 4.27-8.91%) and 26.54% (95% CI: 20.89-32.2%), respectively. Conclusion: This present study provides the exact prevalence of EML4-ALK rearrangement in different variants for NSCLC patients with ALK positive.