Tumors morphologically classified as pigmented epithelioid melanocytomas (PEMs) are genomically diverse, with the 2 most common genomic subtypes being PRKC fusions or PRKAR1A inactivating mutations. PRKC fusions activate the Gα q/11 pathway similar to blue nevi. Conversely, inactivating mutations in PRKAR1A activate the Gα s pathway. We hypothesize that PRKC fusions have greater genomic overlap with blue nevi compared with PRKAR1A-inactivated PEMs. We characterized the clinical and morphologic features of 21 PRKC and PRKACB fusion melanocytic tumors and compared this to PRKAR1A mutated PEMs. To test our hypothesis regarding greater genomic overlap between PRKC fusions and blue nevi relative to PRKAR1A mutated PEMs, we performed a principal component analysis (PCA) using mRNA expression data. Lastly, we performed a meta-analysis focusing on the outcome data of PRKC fusions. PRKC fusions occur at a younger median age than PRKAR1A mutated PEMs (16 vs. 27). Histologically, PRKC fusions have solid aggregates of epithelioid melanocytes not typical of PRKAR1A mutated PEMs. The PCA plot showed no overlap between the PRKC fusion group and the PRKAR1A-mutated PEMs. There was a significant overlap between PRKC fusions and blue nevi. A meta-analysis of PRKC fusion cases in the literature suggests melanoma is uncommon, but the loss of BAP-1 nuclear expression may be associated with an adverse prognosis as in tumors from the blue nevus family. PRKC fusion melanocytic tumors have greater genomic overlap with blue nevi compared with PRKAR1A mutated PEMs. We recommend categorizing benign PRKC fusion melanocytic tumors as blue fusion nevi/tumors.

Poly (ADP- ribose) polymerase inhibitors (PARPi) has been increasingly adopted for metastatic castration-resistance prostate cancer (mCRPC) patients with homologous recombination repair deficiency (HRD). However, it is unclear which PARPi is optimal in mCRPC patients with HRD in 2nd -line setting.

Many studies have demonstrated the relationship between METTL3 protein expression and clinical outcomes in various cancers and elucidated the mechanism by which METTL3 disrupts the behavior of cancer cells. Here, we attempted to define the prognostic value of METTL3 protein in patients with cancer via systematic analysis and explored the potential effect of inhibiting METTL3 using its specific inhibitor.

Numerous studies have investigated the association between CDH1 polymorphisms and gastric cancer (GC) risk. However, the results have been inconsistent and controversial. To further determine whether CDH1 polymorphisms increase the risk of GC, we conducted a meta-analysis by pooling the data.

Recent trials show 5-year survival rates >95% for ETV6::RUNX1 Acute Lymphoblastic Leukemia (ALL). Since treatment has many side effects, an overview of cumulative drug doses and intensities between eight international trials is presented to characterize therapy needed for cure. A meta-analysis was performed as a comprehensive summary of survival outcomes at 5 and 10 years. For drug dose comparison in non-high risk trial arms, risk group distribution was applied to split the trials into two groups: trial group A with ~70% (range: 63.5-75%) of patients in low risk (LR) (CCLSG ALL2004, CoALL 07-03, NOPHO ALL2008, UKALL2003) and trial group B with ~45% (range: 38.7-52.7%) in LR (AIEOP-BFM ALL 2000, ALL-IC BFM ALL 2002, DCOG ALL10, JACLS ALL-02). Meta-analysis did not show evidence of heterogeneity between studies in trial group A LR and medium risk (MR) despite differences in treatment intensity. Statistical heterogeneity was present in trial group B LR and MR. Trials using higher cumulative dose and intensity of asparaginase and pulses of glucocorticoids and vincristine showed better 5-year event-free survival but similar overall survival. Based on similar outcomes between trials despite differences in therapy intensity, future trials should investigate, to what extent de-escalation is feasible for ETV6::RUNX1 ALL.

The leptin receptor, encoded by the LEPR gene, is involved in tumorigenesis. A potential functional variant of LEPR, rs1137101 (Gln223Arg), has been extensively investigated for its contribution to the risk of digestive system (DS) cancers, but results remain conflicting rather than conclusive. Here, we performed a case-control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk.

Hepatocellular carcinoma is the most common type of liver cancer, accounting for 70% to 85% of individuals with primary liver cancer. Gene therapy, which uses genes to treat or prevent diseases, holds potential for treatment, especially for tumours. Trials on the effects of gene therapy in people with hepatocellular carcinoma have been published or are ongoing.

Globally, non-small cell lung cancer (NSCLC) is the primary cause of cancer-related mortality, both early and accurate diagnosis are essential for effective treatment and improved patient outcomes. Exosomal noncoding RNAs (ncRNAs) have emerged as promising biomarkers for NSCLC diagnosis. This meta-analysis aims to assess the diagnostic accuracy of exosomal long noncoding RNAs (lncRNAs) for diagnosing NSCLC.

Prostate cancer is one of the most common types of cancer in the US, and it has a high mortality rate. Diabetes mellitus is also a dangerous health condition. While some studies have examined the relationship between diabetes mellitus and the risk of prostate cancer, there is still some debate on the matter. This study aims to carefully assess the relationship between prostate cancer and diabetes from both real-world and genetic-level data.

Objectives: Exploring the relationship between the hOGG1 rs1052133 polymorphism and the occurrence of nasopharyngeal carcinoma (NPC). Methods: PubMed, Web of Science, Scopus, CNKI, Wanfangdata, and VIP were used to search for studies and the NOS evaluation scale was used to evaluate the quality. All studies were grouped according to different genotypes. The Cochrane's Q test and I2 test were used for heterogeneity evaluations. If heterogeneity was small, the fixed effects model was used, and conversely, the random effects model was used. Publication bias was also detected. P < .05 in all results indicated statistically significant. Results: We ultimately included 6 studies with 2021 NPC patients in the study group and 2375 healthy populations in the control group. After meta-analysis, it was found that the total OR value of the "Ser/Cys (CG) vs Ser/Ser (CC)" group was 1.00 (95% CI: 0.85-1.18) and the "Cys/Cys (GG) vs Ser/Ser (CC)" group was 1.06 (95% CI: 0.87-1.28). These results were not statistically significant (P > .05). Furthermore, the integrated total OR values of each group were not statistically significant with or without the smoking history, even in other genotype models (Allele, Dominant, Recessive, and Additive) (P > .05). Conclusion: There is no clear correlation between the hOGG1 rs1052133 polymorphism and the occurrence of NPC, even with or without the smoking history.

Vitamin D acts through the vitamin D receptor (VDR), and vitamin D level decreases in multiple myeloma (MM) patients. Single nucleotide polymorphisms in VDR alter its functions to affect the vitamin D status. This raises the question of whether VDR gene polymorphisms are associated with MM risk, which has been investigated in case‒control studies, but the results have been inconsistent. This meta-analysis aimed to investigate the relationship between VDR gene polymorphisms and MM risk. The PubMed, Web of Science, Medline, Embase, Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journal (VIP), Wanfang Databases (WANFANG) were searched from inception to June 1, 2023, without language restriction or publication preference. Pooled odds ratio (OR) and 95% confidence interval (CI) for each variable were calculated. Leave-one-out sensitivity analysis was performed to determine the source of heterogeneity. Publication bias was assessed using Begg' and Egger's tests, and the trim-and-fill method was used to compensate for publication bias. The correlation meta-analysis was conducted using Comprehensive Meta-Analysis 3.0 and STATA 12.0 software. All the included studies were based on Asian populations and involved four VDR gene polymorphisms, TaqI (rs731236), ApaI (rs7975232), BsmI (rs1544410) and FokI (rs2228570). The results showed that TaqI (C vs. T: OR = 1.487, 95% CI 1.052, 2.104, P = 0.025; CC + CT vs. TT: OR = 1.830, 95% CI 1.138, 2.944, P = 0.013), ApaI (T vs. G: OR = 1.292, 95% CI 1.101, 1.517, P = 0.002; TT vs. GG: OR = 1.600, 95% CI 1.106, 2.314, P = 0.013; TG vs. GG: OR 1.305, 95% CI 1.050, 1.622; P = 0.016; TT + TG vs. GG: OR = 1.353, 95% CI 1.103, 1.662, P = 0.004), BsmI (GG vs. AA: OR = 1.918, 95% CI 1.293, 2.844, P = 0.001; GA vs. AA: OR = 1.333, 95% CI 1.058, 1.679, P = 0.015; G vs. A: OR = 1.398, 95% CI 1.180, 1.657, P = 0.000; GG vs. AA + GA: OR = 1.686, 95% CI 1.174, 2.423, P = 0.005), and FokI (T vs. C: OR = 1.687, 95% CI 1.474, 1.931, P = 0.000; TT vs. CC: OR = 2.829, 95% CI 2.066, 3.872, P = 0.000; TC vs. CC: OR = 1.579, 95% CI 1.304, 1.913, P = 0.000, TT + TC vs. CC: OR = 1.771, 95% CI 1.477, 2.125, P = 0.000; TT vs. CC + TC: OR = 2.409, 95% CI 1.814, 3.200, P = 0.000) are associated with MM risk. VDR gene polymorphisms including ApaI, BsmI, TaqI, and FokI are associated with MM risk in Asian populations. Additional studies with large sample sizes and different ethnicities are needed.

Over recent years, there has been a notable rise in the incidence of intrahepatic cholangiocarcinoma (iCCA), which presents a significant challenge in treatment due to its complex disease characteristics and prognosis. Notably, the identification of fibroblast growth factor receptor 2 (FGFR2) fusion/rearrangement, a potential oncogenic driver primarily observed in iCCA, raises questions about its impact on the prognostic outcomes of patients undergoing surgical intervention or other therapeutic approaches.

The mechanisms underlying alcohol-induced breast carcinogenesis are not fully understood but may involve hormonal changes.

We investigated whether an observed reduction in overall childhood cancer risk (<15 years of age) in twins has been sustained, and how this extends into young adulthood. We searched for English language publications reporting childhood cancer risk in twins, obtained unpublished data directly from some authors, and updated a meta-analysis. We used the Swedish Multigeneration Register to investigate the age to which the reduced overall risk of childhood cancer (observed previously using that Swedish dataset and in this and earlier meta-analyses) persisted into the teenage/young adult years, and which specific tumors accounted for the overall risk reduction beyond childhood. Our meta-analysis of studies of aggregate childhood cancer risk in twins confirmed their approximate 15% reduction in cancer mortality and incidence. Further analysis of Swedish Multigeneration Register data for 1958 to 2002 suggested these reduced risks of cancer (particularly leukaemias and renal tumors) extended from childhood to young adult ages. Reduced risks of these and some other specific tumor types occurring across childhood/teenage/young adult years appeared to account for most of the overall risk reduction. Our results suggest a persistent reduction of overall childhood cancer risk in twins and that this extends into young adulthood. Risk reductions for several specific tumors might account for this and, although there are several potential explanations, intrauterine growth patterns of twins might be a major contributor.

Multi-gene panel testing allows many cancer susceptibility genes to be tested quickly at a lower cost making such testing accessible to a broader population. Thus, more patients carrying pathogenic germline mutations in various cancer-susceptibility genes are being identified. This creates a great opportunity, as well as an urgent need, to counsel these patients about appropriate risk-reducing management strategies. Counseling hinges on accurate estimates of age-specific risks of developing various cancers associated with mutations in a specific gene, ie, penetrance estimation. We propose a meta-analysis approach based on a Bayesian hierarchical random-effects model to obtain penetrance estimates by integrating studies reporting different types of risk measures (eg, penetrance, relative risk, odds ratio) while accounting for the associated uncertainties. After estimating posterior distributions of the parameters via a Markov chain Monte Carlo algorithm, we estimate penetrance and credible intervals. We investigate the proposed method and compare with an existing approach via simulations based on studies reporting risks for two moderate-risk breast cancer susceptibility genes, ATM and PALB2. Our proposed method is far superior in terms of coverage probability of credible intervals and mean square error of estimates. Finally, we apply our method to estimate the penetrance of breast cancer among carriers of pathogenic mutations in the ATM gene.

A tyrosine-kinase inhibitor (TKI) is indicated as a first-line treatment for patients with non-small-cell lung cancer (NSCLC) harboring an epidermal growth-factor - receptor (EGFR) mutation. Chemotherapy (ChT) given in combination with an EGFR-TKI in this setting is of interest.

Familial Pancreatic Cancer (FPC) presents a notable risk, with 3-10% of pancreatic adenocarcinoma cases having a family history. Studies link FPC to syndromes like HBOC, suggesting BRCA1/BRCA2 mutations play a role. BRCA gene functions in DNA repair impact FPC management, influencing sensitivity to therapies like PARP inhibitors. Identifying mutations not only aids FPC treatment but also reveals broader cancer risks. However, challenges persist in selectively applying genetic testing due to cost constraints. This Systematic Review focuses on BRCA1/BRCA2 significance in FPC, diagnostic criteria, prognostic value, and limitations.

Circulating tumour DNA (ctDNA) has emerged as a promising biomarker in various cancer types, including locally advanced rectal cancer (LARC), offering potential insights into disease progression, treatment response and recurrence. This review aims to comprehensively evaluate the utility of ctDNA as a prognostic biomarker in LARC.

C-X-C motif chemokine ligand (CXCL8), also known as interleukin-8, is a prototypical CXC family chemokine bearing a glutamic acid-leucine-arginine (ELR) motif that plays key roles in the onset and progression of a range of cancers in humans. Many prior studies have focused on exploring the relationship between CXCL8 gene polymorphisms and the risk of cancer. However, the statistical power of many of these reports was limited, yielding ambiguous or conflicting results in many cases.

Genetic variants in Epstein-Barr virus (EBV) have been strongly associated with nasopharyngeal carcinoma (NPC) in South China. However, different results regarding the most significant viral variants, with polymorphisms in EBER2 and BALF2 loci, have been reported in separate studies. In this study, we newly sequenced 100 EBV genomes derived from 61 NPC cases and 39 population controls. Comprehensive genomic analyses of EBV sequences from both NPC patients and healthy carriers in South China were conducted, totaling 279 cases and 227 controls. Meta-analysis of genome-wide association study revealed a 4-bp deletion downstream of EBER2 (coordinates, 7188-7191; EBER-del) as the most significant variant associated with NPC. Furthermore, multiple viral variants were found to be genetically linked to EBER-del forming a risk haplotype, suggesting that multiple viral variants might be associated with NPC pathogenesis. Population structure and phylogenetic analyses further characterized a high risk EBV lineage for NPC revealing a panel of 38 single nucleotide polymorphisms (SNPs), including those in the EBER2 and BALF2 loci. With linkage disequilibrium clumping and feature selection algorithm, the 38 SNPs could be narrowed down to 9 SNPs which can be used to accurately detect the high risk EBV lineage. In summary, our study provides novel insight into the role of EBV genetic variation in NPC pathogenesis by defining a risk haplotype of EBV for downstream functional studies and identifying a single high risk EBV lineage characterized by 9 SNPs for potential application in population screening of NPC.