Histology restricted genetic predisposition testing of ovarian carcinoma patients is a topic of debate as the prevalence of BRCA1/2 pathogenic variants (PVs) in various histological subtypes is ambiguous. Our primary aim was to investigate the proportion of germline BRCA1/2 PVs per histological subtype. Additionally, we evaluated (i) proportion of somatic BRCA1/2 PVs and (ii) proportion of germline PVs in other ovarian carcinoma risk genes.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. Chemerin, a novel adipokine, is involved in inflammation, energy metabolism, adipogenesis, angiogenesis and insulin secretion in the adipose cells and ovary. This systematic review with meta-analysis aimed to compare serum and follicular fluid (FF) chemerin and ovarian chemerin mRNA expression among women with PCOS and non-PCOS.

In the last decades the association of leukocyte telomere length (LTL) and mitochondrial copy number (mtDNAcn) with cancer risk has been the focus of many reports, however the relation is not yet completely understood. A meta-analysis of 112 studies including 64,184 cancer cases and 278,641 controls that analysed LTL and mtDNAcn in relation to cancer risk has been conducted to further our understanding of the topic. Stratified analyses for tumor type were also performed. Overall, no association was observed for all cancer combined neither for LTL nor mtDNAcn. Significant associations were detected for these biomarkers and specific cancer type; however, a large degree of heterogeneity was present, even within the same tumor type. Alternatives approaches based on polymorphic variants, such as polygenic risk scores and mendelian randomization, could be adopted to unravel the causal correlation of telomere length and mitochondrial copy number with cancer risk.

The purpose of this study was to explore the association of IL-10 polymorphisms with susceptibility to colorectal cancer (CRC) and gastric cancer (GC).

The CXC chemokines belong to a unique family of cytokines that participates in the progression and development of many malignant tumors. Evidence for the relationship between chemokine (C-X-C motif) receptor 2 (CXCR2) C1208T polymorphism and susceptibility to cancer remains inconsistent.

Importance: The protein p53 is an unequivocal tumor suppressor that is altered in half of all cancers. The immune system produces systemic p53 autoantibodies (p53 Abs) in many cancer patients. Objective: This systemic review and meta-analysis focuses on the prognostic value of p53 Abs expressed in the serum of patients with solid tumors. Data Sources: All the clinical investigations were searched on PubMed from the first study dated 1993 until May 2021 (date of submission of the manuscript). Study Selection: Studies were included that met the following criteria: (1) participants with cancer; (2) outcome results expressed in relation to the presence of a p53 antibody; (3) a primary outcome (disease-free survival, overall survival or progression-free survival) expressed as hazard ratio (HR). The following exclusion criteria were used: (1) insufficient data available to evaluate outcomes; (2) animal studies; (3) studies with less than 10 participants. As a result, 12 studies were included in the analysis. Data Extraction and Synthesis: PRISMA guidelines were used for abstracting and assessing data quality and validity by three independent observers. The summary estimates were generated using a fixed-effect model (Mantel-Haenszel method) or a random-effect model (DerSimonian-Laird method), depending on the absence or presence of heterogeneity (I2). Main Outcome(s) and Measure(s): The primary study outcome was to determine the prognostic value of p53 Abs from a large population of patients with solid tumors, as determined before data collection. Results: In total, 12 clinical studies involving 2094 patients were included in the meta-analysis, and it was determined that p53 Abs expression in the serum significantly correlated with poorer survival outcomes of cancer patients (95% CI 1.48 [1.24, 1.77]; p < 0.00001). Conclusions and Relevance: This is the first meta-analysis proving the diagnostic utility of p53-Abs for cancer patients in predicting poorer outcomes. The serum-p53 value (s-p53-value) may be useful for future theranostics.

Background and objective:N-acetyltransferases 1 and 2 (NAT1 and NAT2) genes have polymorphisms in accordance with slow and rapid acetylator phenotypes with a role in the development of head and neck cancers (HNCs). Herein, we aimed to evaluate the association of NAT1 and NAT2 polymorphisms with susceptibility to HNCs in an updated meta-analysis. Materials and methods: A search was comprehensively performed in four databases (Web of Science, Scopus, PubMed/Medline, and Cochrane Library until 8 July 2021). The effect sizes, odds ratio (OR) along with 95% confidence interval (CI) were computed. Trial sequential analysis (TSA), publication bias and sensitivity analysis were conducted. Results: Twenty-eight articles including eight studies reporting NAT1 polymorphism and twenty-five studies reporting NAT2 polymorphism were involved in the meta-analysis. The results showed that individuals with slow acetylators of NAT2 polymorphism are at higher risk for HNC OR: 1.22 (95% CI: 1.02, 1.46; p = 0.03). On subgroup analysis, ethnicity, control source, and genotyping methods were found to be significant factors in the association of NAT2 polymorphism with the HNC risk. TSA identified that the amount of information was not large enough and that more studies are needed to establish associations. Conclusions: Slow acetylators in NAT2 polymorphism were related to a high risk of HNC. However, there was no relationship between NAT1 polymorphism and the risk of HNC.

Colorectal cancer (CRC) can be classified according to the chromosomal-instability pathway (a microsatellite-stable (MSS) pathway) and the microsatellite-instability (MSI) pathway. Adjuvant therapy after surgery in advanced CRC is usually based on fluoropyrimidine 5-fluorouracil (5-FU) alone or combined with other agents. Controversy however remains on the use of 5-FU-based regimens in treating MSI-related tumours.

Germline mutations in several genes, mainly DNA repair genes, have been associated with prostate cancer (PCa) progression. However, primarily due to the rarity of mutations, statistical evidence for these associations is not consistently established. The objective of this study is to synthesize evidence from multiple studies using a meta-analysis.

Controversial results existed in amounts of studies investigating the authentic association of estrogen receptor genes (ESR1 and ESR2) polymorphisms with the occurrence and progression of polycystic ovary syndrome (PCOS). The inconsistency might result from different loci, sample sizes, and ethnicities. To find the potential correlations between ESR1/ESR2 polymorphisms and PCOS risk, we conducted the first systematic review and meta-analysis to comprehensively summarize current studies in a large combined population.

For colorectal cancer patients, traditional biomarker deficient mismatch repair/microsatellite instability (dMMR/MSI) is an accurate predictor of immune checkpoint inhibitors (ICIs). Recent years, researchers considered tumor mutation burden (TMB) as another predictive biomarker which means the number of nonsynonymous mutations in cancer cells. Several studies have proven that TMB can evaluate the efficacy of ICI therapy in diverse types of cancer, especially in non-small cell lung cancer and melanoma. However, studies on the association between TMB and the response to ICI therapy in colorectal cancer alone are still lacking. In this study, we aim to verify the effect of TMB as a biomarker in predicting the efficacy of ICIs in colorectal cancer.

To investigate O-6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation in humoral tissue as biomarker for lung cancer diagnosis by pooling relevant open published data.

Nasopharyngeal carcinoma (NPC) is a cancer of epithelial origin with a high incidence in certain populations. While NPC has a high remission rate with concomitant chemoradiation, recurrences are frequent, and the downstream morbidity of treatment is significant. Thus, it is imperative to find alternative therapies.

To investigate the potential correlation between the Arg188His (rs3218536) polymorphism of X-ray repair cross-complementing 2 (XRCC2) and colorectal cancer (CRC) risk, as the association remains unclear.

Tumor necrosis factor alpha (TNF-α) is a cytokine with a key role in proinflammation and multiple diseases, including cancer. The gene encoding TNF-α is located within a highly polymorphic region on chromosome 6p21.3; two polymorphisms -308G/A (rs1800629) and -238G/A (rs361525) have been associated with occurrence of human diseases. There is a debate in recent meta-analyses that reached discrepant conclusions regarding the potential role of TNF-α polymorphisms in multiple myeloma (MM) risk. The aim of this systematic review and meta-analysis is to investigate the association between the aforementioned two polymorphisms with the risk and survival of MM.

OncotypeDX® recurrence score (RS) aids therapeutic decision-making in oestrogen-receptor-positive (ER+) breast cancer. Radiomics is an evolving field that aims to examine the relationship between radiological features and the underlying genomic landscape of disease processes. The aim of this study was to perform a systematic review of current evidence evaluating the comparability of radiomics and RS.

Preliminary clinical evidence suggests a detrimental effect of pathogenic variants of BRCA1 and 2 genes on fertility outcome. This meta-analysis evaluates whether women carrying BRCA mutations (BRCAm) have decreased ovarian reserve, in terms of Anti-Muellerian Hormone (AMH), compared to women without BRCAm (wild-type).

Breast cancer has four distinct molecular subtypes which are discriminated using gene expression profiling following biopsy. Radiogenomics is an emerging field which utilises diagnostic imaging to reveal genomic properties of disease. We aimed to perform a systematic review of the current literature to evaluate the value radiomics in differentiating breast cancers into their molecular subtypes using diagnostic imaging.

Previously, we have reported that the dysregulation of ketogenesis plays an important role in the carcinogenesis of clear cell renal cell carcinoma (ccRCC). Here, we demonstrate decreased expression of the HMGCS2 gene in ccRCC, a critical enzyme for the synthesis of the ketone body β-hydroxybutyrate (β-OHB). We found that the reduced transcription of the HMGCS2 gene in ccRCC cells was significantly correlated to a higher relative methylation rate in its promotor region. The higher methylation rate in the region of the transcription start site and 1st exon of the HMGCS2 gene was, in turn, correlated with a worse clinical outcome for patients. The transcription of HMGCS2 was possible to restore by treatment with 5-aza-2'-deoxycytidine and with the histone deacetylase inhibitor β-OHB. Therefore, the low levels of the HMGCS2 enzyme in ccRCC may be the consequence of hypermethylation of the HMGCS2 promotor. The ensuing reduction in the ketone body levels further suppresses the transcription of HMGCS2 via a feedback loop. Ectopic expression of HMGCS2 attenuates the migration and invasion of ccRCC but does not affect the proliferative capacity of ccRCC cells in vitro. In addition, we showed that ectopic expression of HMGCS2 boosts the intracellular levels of β-OHB and that exogenously applied β-OHB suppresses the motility and invasion of ccRCC. Our study reveals crosstalk between genes that regulate metabolism and their metabolites, thus providing a better understanding of the epigenetic mechanism involved in ccRCC carcinogenesis and suggesting opportunities for metabolic therapy of tumors. Initially, we suggest that the mRNA level of HMGCS2 could serve as a potentially valuable diagnostic (AUC = 0.918, p < 0.001) and prognostic biomarker.

Osteosarcoma is the most prevalent malignant osseous sarcoma in children and adolescents, whose prognosis is still relatively poor nowadays. Recent studies have shown the critical function and potential clinical applications of circular RNAs (circRNAs) in osteosarcoma. Our review aimed to perform an updated meta-analysis to explore their clinicopathologic significance and prognostic value.