The effect of single-nucleotide polymorphisms (SNPs) in Cyclin Dependent Kinase Inhibitor 1A (CDKN1A C/A), Mouse Double Minute 2 (MDM2), 309 T/G methylenetetrahydrofolate reductase (MTHFR) 677 C/T, MTHFR 1298 A/C, and Methionine synthase (MTR) 2756 A/G has been investigated in retinoblastoma (RB) with inconsistent results. Therefore, this study aims to conduct a meta-analysis and explore the overall role of these genetic variants with retinoblastoma risk. Literature search was done using PubMed, EMBASE, Cochrane Library, Google, Dogpile, and CBM all studies evaluating the association between CDKN1A or p21 C/A, MDM2 309 T/G, MTHFR 677 C/T, MTHFR 1298 A/C, and MTR 2756 A/G polymorphism and RB risk were included. A total of 1773 patients and 2474 controls were included. To understand these polymorphisms' role in RB risk, pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random or fixed effects model. P values < 0.05 were considered statistically significant. Funnel plots were used to assess publication bias. Our meta-analysis showed a significant association between RB susceptibility to CDKN1A dominant model (OR = 1.518, 95% CI = 1.003-2.298, P = 0.048), MDM2 dominant model (OR = 0.700, 95% CI = 0.542-0.903, P = 0.006) and MTR 2756 A/G all models that is allele model (OR = 4.680, 95% CI = 1.992-10.993, P = 0.000), dominant model (OR = 2.044, 95% CI = 1.511-2.765, P = 0.000), and recessive model (OR = 0.283, 95% CI = 0.122-0.656, P = 0.003). The present meta-analysis suggested that MTR 2756 A/G, MDM2 309 T/G, and CDKN1A polymorphism are associated with the risk of RB.

Pre-therapeutic UGT1A1 genotyping is increasingly performed in patients receiving irinotecan, as its active metabolite SN-38 is primarily cleared through UGT1A1-mediated glucuronidation. Patients with the UGT1A1*28/*28 genotype exhibit reduced UGT1A1 activity, leading to increased SN-38 exposure and a higher risk of adverse events such as neutropenia and diarrhea. Although sacituzumab govitecan contains the same active metabolite as irinotecan, routine UGT1A1 genotyping prior to treatment with this drug is not yet standard practice and is not included in its product information. The aim of this study was to assess whether pre-therapeutic UGT1A1 genotyping may also benefit patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative and triple-negative breast cancer who are treated with sacituzumab govitecan. A literature search was conducted to identify relevant studies assessing the impact of UGT1A1 genotyping on the safety and efficacy of sacituzumab govitecan treatment. A meta-analysis was performed on selected studies. Additionally, a pharmacological analysis was performed using public data comparing SN-38 levels in patients treated with sacituzumab govitecan to those receiving irinotecan. The meta-analysis shows that grade ≥ 3 adverse events, including neutropenia, febrile neutropenia, and diarrhea, occurred more frequently in patients with the *28/*28 genotype. Furthermore, a statistically significant increased risk was found for developing grade ≥ 3 diarrhea or febrile neutropenia in this group. Although the meta-analysis was underpowered due to small sample sizes, the pharmacological analysis demonstrated higher SN-38 levels in patients treated with sacituzumab govitecan, supporting the rationale for UGT1A1 genotyping in this context.

Matrix metalloproteinases (MMPs) are a group of genes that play a crucial role in cancer progression. In this study, we conducted a systematic review and meta-analysis to evaluate the association between gelatinase polymorphisms (specifically MMP2 and MMP9) and lung cancer (LC) susceptibility.

Lysophosphatidic acid receptor 1 (LPAR1) mediates various biological behaviors in physiological and pathological processes. This study aims to comprehensively evaluate the prognostic value of LPAR1 expression and methylation in LGG, and explore their functional effects on tumor progression and immune regulation.

MicroRNA-related single nucleotide polymorphisms (miRNA-SNPs) influence post-transcriptional gene regulation and may contribute to breast cancer susceptibility. Individual case-control studies have evaluated several miRNA-SNPs, but there is limited or no pooled evidence available for many variants.

Helicobacter pylori (H. pylori) is a major risk factor for gastric cancer (GC) and multiple other chronic illnesses. Host genetic factors influence the susceptibility to H. pylori infection, as evidenced by elevated concordance in monozygotic twins and racial disparities independent of socioeconomic status. Leveraging meta-analyses and in silico functional annotation, we investigated host genetic susceptibility to H. pylori infection, and to examine how these variants may influence gastric cancer (GC) risk.

Gastric cancer (GC) is the fifth leading cause of cancer-related death worldwide, with a median overall survival of approximately 12 months. The proto-oncogene c-MYC is among the most frequently activated oncogenes, implicated in roughly 20% of all malignancies.

The increasing global incidence of thyroid cancer highlights the importance of accurately assessing risk factors, particularly those related to family history. Although having affected family members is widely recognized as a risk factor for thyroid cancer, the exact degree of risk and its variation across types of familial relationships, parental gender, and geographic regions remain unclear. This systematic review and meta-analysis aimed to clarify the association between family history and thyroid cancer risk. We conducted a comprehensive literature search of PubMed, Web of Science, and Embase following PRISMA guidelines, identifying 13 studies from 503 initially screened. Statistical analyses were performed using random-effects models to estimate pooled odds ratios and risk ratios, with subgroup analyses to assess variations across population and relationship types. Our findings showed an approximately 4.5-fold higher risk of thyroid cancer in individuals with affected family members. Individuals with affected siblings were more likely to develop thyroid cancer while the risks associated with maternal and paternal family history were comparable in magnitude, with no statistical difference between them. Socioeconomic, educational, and lifestyle differences did not significantly influence risk, and geographic variations in familial risk could not be statistically confirmed by the subgroup analysis, in the context of high between-study heterogeneity. These results suggest that family history is a substantial risk factor for thyroid cancer, reinforcing the need for enhanced surveillance and screening strategies for those with a familial predisposition.

BRCA1 and BRCA2 are tumor suppressor genes essential for DNA repair. Mutations in these genes significantly increase breast (BC) and ovarian cancer (OC) risk, with BRCA1-positive facing a 70% BC and 40% OC lifetime risk. While guidelines for BRCA-positive are well established, recommendations for BC surveillance in BRCA-patients already diagnosed with OC remain limited. This meta-analysis evaluates BC risk post-OC in BRCA-mutated women.

We conducted a comprehensive assessment of the prognostic significance of CDK1 expression in patients diagnosed with cancer. Pooled hazard ratios (HRs), odds ratios (ORs), and 95 % confidence interval (CI) were calculated to determine the associations between CDK1 expression and overall survival (OS), disease-free survival (DFS), as well as various clinicopathological characteristics. A total of 20 studies, comprising 2470 patients, were included in this meta-analysis. Elevated CDK1 expression was significantly associated with reduced OS in both univariate and multivariate analyses, with pooled HRs of 1.55 (95 % CI: 1.31-1.81) and 1.89 (95 % CI: 1.52-2.36), respectively. Furthermore, higher CDK1 expression levels correlated significantly with adverse pathological features, including tumor size (OR = 1.50; 95 % CI, 1.08-2.09), lymph node metastasis (LNM; OR = 2.41; 95 % CI, 1.69-3.44), higher histological grade (OR = 2.40; 95 % CI, 1.69-3.39) and advanced tumor stage (OR = 1.76; 95 % CI, 1.25-2.48). These findings suggest that CDK1 over-expression may serve as a robust prognostic biomarker associated with unfavorable clinical outcomes in patients with cancer.

Decisions regarding endometrial cancer (EC) adjuvant therapy can be challenging due to the need to balance the benefits of recurrence reduction with treatment toxicity. Circulating tumor DNA (ctDNA) has the potential to guide adjuvant therapy decisions by stratifying patients based on their risk of recurrence.

To investigate the prognostic value of the B-type Raf kinase (BRAF) V600E mutation in papillary thyroid carcinoma.

The impact of epigenetic modifier gene mutations (EMMs) on the prognosis of patients with acute lymphoblastic leukemia (ALL) is controversial, which is unlike AML. A meta-analysis is needed to evaluate the prognostic value of EMMs in ALL. Three databases, including PubMed, EMBase and Web of Science, were retrieved to find out studies exploring the association of EMMs and survival outcomes in ALL. Pooled hazard ratios (HRs) and 95% confidential interval (95%CI) were used to assess the impact of EMMs. Nineteen studies were included in our meta-analysis. DNMT3A mutation was an adverse prognostic factor in overall survival (OS) in patients with ALL (HR, 4.143; P < 0.001) as well as adult T-ALL patients (HR, 3.746; P < 0.001) and those with early T-ALL (HR, 3.523; P = 0.001). IDH mutation also had an unfavorable impact on OS in ALL (HR, 3.583; P < 0.001) and adult T-ALL cohort (HR, 3.562; P < 0.001). For pediatric patients, mutant PHF6 was significantly associated with worse OS in both B-ALL (HR, 3.194; P = 0.026) and T-ALL (HR, 2.125; P = 0.033), while PHF6 mutation had no prognostic impact on the survival of adult T-ALL patients. In addition, patients with KMT2A mutation had shorter OS compared to those with wild type (HR, 4.605; P = 0.045), whereas other EMMs had no impact on prognosis in any type of ALL. Mutations in DNMT3A, IDH, PHF6 and KMT2A showed a significant prognostic effect in ALL or in its specific subtypes, which might contribute to risk stratification and treatment guidance in the management of ALL patients.

BackgroundMYCN gene amplification is associated with poor prognosis in neuroblastoma (NB) patients; however, its detection relies on the invasive fluorescence in situ hybridization technique. Radiomics can non-invasively predict MYCN gene amplification by extracting high-dimensional features from medical images.PurposeTo systematically review and meta-analyze the performance of radiomics models in predicting MYCN gene amplification status in NB patients.Material and MethodsAs of 18 March 2025, a systematic search was performed for original literature on the prediction of MYCN amplification in NB patients using radiomics models in the following databases: PubMed, Embase, Web of Science, and Cochrane Library. The quality of the literature was assessed using the QUADAS-2 and Radiomics Quality Score (RQS) tools. The meta-analysis was performed using the random-effects model.ResultsThis research ultimately included nine articles (899 patients), from which data could be extracted for both radiomics-only models and combined models that integrate radiomic features with other predictors. The radiomics-only model demonstrated pooled sensitivity of 0.85 (95% confidence interval [CI] = 0.77-0.91) and specificity of 0.86 (95% CI = 0.79-0.90), while the combined model showed a sensitivity of 0.81 (95% CI = 0.75-0.87) and specificity of 0.92 (95% CI = 0.87-0.95). Summary receiver operating characteristic (SROC) curve yielded an area under ROC curve of 0.92 ± 0.02 for the radiomics-only model and 0.94 ± 0.02 for the combined model. No evidence of publication bias was found.ConclusionsRadiomics might be one promising approach for predicting MYCN gene amplification in patients with NB.

Dual immune checkpoint inhibitor (ICI) therapy might improve the outcome of adult patients with untreated metastatic BRAF-mutant melanoma. We synthesised the evidence of its effect on overall survival (OS) and adverse events.

Hepatocellular carcinoma (HCC) relapse remains high after curative-intent treatment due to occult minimal residual disease. Circulating tumour DNA (ctDNA) has emerged as a noninvasive biomarker. Systematic search of MEDLINE, EMBASE and the Cochrane Library up to November 2024 identified studies evaluating plasma ctDNA in non-metastatic HCC patients undergoing curative-intent treatment. Hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrence-free survival (RFS) and overall survival (OS) were pooled using random-effects models; sensitivity and specificity for predicting recurrence were summarised. Ten retrospective studies (n = 793) met inclusion criteria. Postoperative ctDNA positivity was associated with shorter RFS (HR 4.48; 95% CI 2.56-7.82; I² = 78%; p < 0.001) and worse OS (HR 2.99; 95% CI 1.94-4.61; I² = 47%; p < 0.001). Baseline ctDNA detection predicted reduced RFS (HR 3.54; 95% CI 1.97-6.38; I² = 35%; p < 0.001). Sensitivity ranged 33-82% and specificity 41-100%, reflecting methodological heterogeneity. Leave-one-out analyses confirmed robustness. Plasma ctDNA is a potent prognostic marker of recurrence and survival in non-metastatic HCC. Prospective trials incorporating ctDNA could optimise postoperative surveillance and guide adjuvant therapy selection.

In patients with early-stage colorectal cancer (CRC), circulating tumor DNA (ctDNA) testing is increasingly used to detect minimal residual disease (MRD) after curative-intent surgery. This information can guide decisions on adjuvant chemotherapy and surveillance. Two main approaches exist, tumor-informed (TI) and tumor-agnostic (TA), however, their diagnostic accuracy in clinical practice remains unclear. We conducted a bivariate diagnostic meta-analysis to compare sensitivity and specificity of TI versus TA ctDNA assays for detecting recurrence in patients with resected CRC. Subgroup analyses were performed based on landmark versus serial sampling strategies. In the serial-sampling setting, TI assays demonstrated markedly higher sensitivity than TA assays (0.88 vs. 0.59; p = 0.001), with no significant differences in false-positive rates. The landmark analyses did not show statistically significant differences between approaches. The results underscore the importance of sampling strategy when selecting a ctDNA test. When longitudinal monitoring is feasible, TI assays provide the most reliable detection of recurrence. This meta-analysis supports tailoring ctDNA testing to the clinical context, prioritizing TI approaches for serial surveillance to better guide adjuvant decision-making and improve patient outcomes.

Sepsis, a potentially fatal condition marked by an abnormal immune response, is likewise noted during the development of malignant skin tumors. However, it remains uncertain whether there is a causal link between malignant skin tumors and sepsis. A bidirectional 2-sample Mendelian randomization (MR) analysis was performed utilizing data from the most comprehensive genome-wide association studies on malignant skin neoplasms, involving 218,792 participants, along with genome-wide association studies data from the UK Biobank cohort (N = 486,484; comprising 1896 sepsis cases and 484,558 controls). The inverse-variance weighted method served as the primary analytical approach, complemented by 4 additional MR techniques (MR-Egger, weighted median, and weighted mode) for sensitivity assessments. Heterogeneity was evaluated using Cochran Q test. To verify the robustness of the MR findings, a leave-one-out analysis was conducted. The Bonferroni correction was applied to assess the strength of causal associations. Finally, data from the FinnGen study and the UK Biobank cohort were synthesized through meta-analysis. In the primary inverse-variance weighted analysis, genetically predicted malignant skin neoplasms were significantly associated with sepsis (odds ratio = 1.14, 1.12, 1.14, 1.12; 95% confidence interval: 1.04-1.26, 1.01-1.23, 1.04-1.25, 1.01-1.23; P < .001 or P = .03). These results were consistent across sensitivity analyses, and no evidence of directional pleiotropy was observed (MR-Egger intercept: P = .15). Moreover, genetically predicted sepsis showed no causal effect on the development of malignant skin neoplasms. The results of this study suggest that malignant skin neoplasms may be a risk factor for sepsis and could contribute to the progression of the condition.

To comprehensively evaluate the efficacy and safety of neoadjuvant therapy combined with immunotherapy in patients with MMR-proficient/microsatellite stable (pMMR/MSS) non-metastatic rectal cancer.

Mismatch repair deficient (MMRd) endometrial carcinomas (EC) constitute 30 % of ECs and emerging evidence suggests that MLH1 promoter hypermethylated (MLH1ph) tumours may be more aggressive than previously recognized. This study aimed to evaluate overall survival (OS) and progression-free survival (PFS) in MLH1ph ECs compared to non-MLH1ph MMRd ECs.