Breast cancer is the most common cancer diagnosed in women. Increased exposure to oestrogens is one of the major risk factors for breast cancer. The synthesis of estrogens is mediated by the aromatase enzyme that encoded by CYP19A1 gene. Further, highest aromatase activities were documented in tumor-associated stroma tissues of breast. Genetic polymorphisms in CYP19A1 gene are known to modulate the estradiol and to the estradiol/testosterone ratio. The rs10046 T>C polymorphism in the 3' untranslated region of CYP19A1 gene has been linked to the risk of breast cancer. The studies conducted till date are not consistent in reporting the association of rs10046 polymorphism with breast cancer. In the present study, we have conducted a meta-analysis of data available for CYP19A1 rs10046 T>C and breast cancer from 23 studies. The outcome of the present meta-analysis showed that there is no association between rs10046 polymorphism and breast cancer risk in all genetic models [C vs. T: odds ratio (OR) = 0.99, confidence interval (CI) = 0.88-1.23; CC vs. TC + TT: OR = 1.02, CI = 0.88-1.18; TC + CC vs. GG: OR = 0.97, CI = 0.80-1.17]. Further, ethnicity based subgroups also failed to show the association between breast cancer and rs10046. Begg's funnel plots and Egger's tests did not reveal evidence for publication bias (Egger's P value = 0.832). In summary, the rs10046 T>C polymorphism on CYP19A1 is not a major risk factor for breast cancer.

Myasthenia gravis (MG), an autoimmune condition known for impairing neuromuscular signaling, has increasingly been implicated in broader neurological dysfunctions. Recent studies point toward a possible connection between autoimmune and neurodegenerative processes. However, whether MG contributes causally to the onset of major neurodegenerative disorders such as Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS) remains unclear. This study utilizes Mendelian randomization (MR) to explore the potential causal influence of MG on these disorders from a genetic standpoint. A univariable Mendelian randomization (UVMR) framework was employed using summary-level data from genome-wide association studies (GWAS) to evaluate the effect of MG on the risk of AD, PD, and ALS. To confirm the robustness of the association between MG and AD, 2 independent AD GWAS datasets were incorporated for external replication, followed by a meta-analysis to combine the evidence. Additionally, multivariable Mendelian randomization (MVMR) was conducted to adjust for smoking behavior as a potential confounding factor. The UVMR analysis revealed a statistically significant causal relationship between MG and increased susceptibility to AD (odds ratio (OR): 1.037; 95% confidence interval (CI): 1.007-1.068; P = .016). No significant causal effects were observed for PD (OR: 1.019; 95% CI: 0.964-1.077; P = .509) or ALS (OR: 1.055; 95% CI: 0.977-1.140; P = .171). The association between MG and AD was consistently validated in 2 independent datasets (ieu-a-297: OR = 1.084; 95% CI: 1.017-1.156; P = .013; ieu-b-2: OR = 1.054; 95% CI: 1.006-1.104; P = .027). Meta-analysis reinforced the evidence supporting MG as a risk factor for AD (OR: 1.047; 95% CI: 1.023-1.072; P < .001). Furthermore, MVMR adjusting for smoking confirmed that MG independently contributes to AD risk (OR: 1.037; 95% CI: 1.006-1.069; P = .020). This study provides robust genetic evidence suggesting that MG is a causal and independent risk factor for AD. These findings highlight a novel link between autoimmunity and neurodegeneration, offering new directions for mechanistic and therapeutic research.

This study aimed to investigate a causal association between Klotho levels and the risk of B-cell lymphoma using a Mendelian randomization (MR) approach. We sought to determine if α-Klotho levels are causally linked to various subtypes of B-cell lymphoma, including diffuse large B-cell lymphoma, follicular lymphoma, Hodgkin lymphoma, and non-Hodgkin lymphoma. We obtained GWAS data for B-cell lymphomas from the FINN Large Cohort in the IEU database and α-Klotho levels from a meta-analysis of GWAS data. The primary analysis employed the inverse-variance weighted method, while sensitivity analyses utilized weighted median, MR-Egger, and weighted mode methods to validate results. Heterogeneity and pleiotropy of genetic instruments were assessed using leave-one-out sensitivity tests, the MR pleiotropy residual sum and outlier test (MR-PRESSO), and Cochran Q test. Our analysis revealed no significant associations between α-Klotho levels and any subtype of B-cell lymphoma using inverse-variance weighted (IVW). The odds ratios and 95% confidence intervals indicated no significant relationship for diffuse large B-cell lymphoma, follicular lymphoma, Hodgkin lymphoma, or unspecified non-Hodgkin lymphoma. Heterogeneity tests and sensitivity analyses supported the robustness of these findings. Our comprehensive MR analysis suggests no causal relationship exists between Klotho levels and the risk of developing B-cell lymphomas.

To systematically evaluate the efficacy and safety of anlotinib plus epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in the treatment of advanced non-small cell lung cancer (NSCLC) with EGFR mutations.

Anaplastic oligodendrogliomas are rare diffuse gliomas. Although radiotherapy (RT) combined with procarbazine, lomustine, and vincristine (PCV) has been the historical standard, temozolomide (TMZ) has been increasingly used.

Pediatric acute myeloid leukemia (AML) is a clinically and genetically heterogeneous malignancy with variable outcomes. Accurate risk stratification based on cytogenetic and molecular markers is essential for guiding therapy. However, the prognostic impact of several key genomic alterations remains inconsistent across studies. This meta-analysis aims to evaluate the prognostic significance of cytogenetic and molecular abnormalities in pediatric AML and clarify their association with survival outcomes.

Prostate cancer (PCa) diagnosis is hampered by the limited specificity of current methods, necessitating more reliable biomarkers. To identify causal protein biomarkers and therapeutic targets in humans, we conducted a proteome-wide Mendelian randomization (MR) study. We first performed a meta-analysis of two independent genome-wide association studies, including 94,397 individuals with PCa and 192,372 controls, which identified five possible susceptibility loci (JAZF1, PDILM5, WDPCP, EEFSEC, TNS3) for PCa. Subsequently, MR and colocalization analyses were performed using genetic instruments for 4907 plasma proteins from deCODE Genetics (N=35,559) and 2940 plasma proteins from UK Biobank Pharma Proteomics Project (UKB-PPP) (N=54,219). Among 3722 human proteins analyzed, 193 were associated with PCa risk, with 20 high-risk proteins (including KLK3) validated across both cohorts. Functional annotation implicated immune and inflammatory responses and cell-cell interaction pathways. Druggability analyses nominated several potential drug targets for PCa, such as HSPB1, RRM2B, and PSCA. Our findings reveal novel risk loci and candidate protein biomarkers, providing new etiological insights and potential avenues for PCa early detection and therapy.

In recent years, an increasing number of observational studies have reported the impact of air pollution on ovarian cancer. However, a Mendelian randomization (MR) study to explore the causal relationship in ovarian cancer has not yet been conducted. This study, based on 2-sample MR, conducts MR analysis by examining 5 air pollution indices with ovarian cancer data from 2 different sources. Subsequently, a meta-analysis of the primary inverse-variance weighted results is performed, followed by multiple corrections on the meta-analysis thresholds to ensure accuracy. Finally, a reverse causality verification of the positive air pollution indices with ovarian cancer is conducted through MR analysis. The MR analysis was conducted using 5 air pollution indices and ovarian cancer data from the Finngen R10 and OpenGWAS databases. A meta-analysis was then performed on the inverse-variance weighted results from both sets of analyses. Multiple corrections were applied to the significance threshold of the meta-analysis results, revealing an odds ratio value of 1.544 (95% confidence interval: 1.180-2.020, P = .0077). Additionally, the positive air pollution index, nitrogen dioxide, showed no reverse causality with ovarian cancer in both data sources. Nitrogen dioxide is a risk factor for ovarian cancer and may increase the risk, accelerating the onset and progression of the disease.

Given that homocysteine (Hey) may be a viable target for intervention and that there is uncertainty regarding the causal relationship between plasma Hcy levels and colorectal cancer (CRC), this study used Mendelian randomization (MR) to investigate the relationship between Hey and CRC. We summarized the data in this work using genome-wide association studies, identified single nucleotide polymorphisms that were strongly correlated with plasma Hcy levels as instrumental variables, and ran MR analysis on 2 separate sets of outcome data. To make sure the results were stable, a meta-analysis was carried out. MR-Egger, weighted median MR analysis, and the inverse variance method were among the specific analysis techniques used. The leave-one-out method, MR-Egger intercept, MR-PRESSO, and Cochran Q test were also used to assess the stability and dependability of the MR analysis results. In 2 separate European population-based datasets (UK Biobank: OR = 0.9992, 95% CI = 0.9963-1.0021, P = .5951, FinnGen: OR = 0.9771, 95% CI = 0.8370-1.1408, P = .7698), inverse variance method analysis did not reveal any significant causal connection between plasma Hcy levels and CRC. The MR-Egger and weighted median analyses yielded nonsignificant relationships. Both the Cochran Q test and the MR-Egger intercept indicated the absence of considerable heterogeneity and horizontal pleiotropy. The conclusions were further corroborated by the results of the MR-PRESSO analysis and leave-one-out. The pooled results of the Meta analysis also failed to demonstrate significant causality (OR = 0.9992, 95% CI = 0.9963-1.0021, P = .5914), therefore providing additional confirmation of the findings from the individual studies. There was no discernible causal relationship between plasma Hcy levels and CRC risk, according to MR analysis. The findings of this study indicate that while Hcy is a possible target for intervention, there may not be a direct causal relationship between it and the risk of CRC. This finding requires further validation in larger sample sizes and in different populations.

This network meta-analysis (NMA) aimed to indicate the most effective first-line therapeutic options for advanced EGFR-mutated NSCLC, particularly considering their specific clinicopathological characteristics.

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide, with cases expected to rise 60% by 2030, especially in Asia. Metastatic CRC (mCRC) has a poor 5-year survival rate of 14%, posing a major treatment challenge. Tumors with DNA mismatch repair deficiency (dMMR) and a high level of microsatellite instability (MSI-H) respond well to immune checkpoint inhibitors (ICIs), shifting treatment strategies. This systematic review and meta-analysis evaluate Pembrolizumab (PEM), Nivolumab (NIV), and Nivolumab plus Ipilimumab (NIV + IPI) for their promising antitumor efficacy in MSI-H/dMMR mCRC.

B7-H4 is an immune-regulatory molecule increasingly recognized for its role in tumor progression and immune evasion in epithelial ovarian cancer. To clarify its clinical relevance, we conducted a systematic review and meta-analysis evaluating the prevalence of B7-H4 expression and its association with survival outcomes. Nineteen eligible studies were included, of which sixteen provided data on expression proportions and eight reported progression-free or overall survival outcomes. The pooled prevalence of high or positive B7-H4 expression was 73%, though with considerable inter-study variability. High B7-H4 expression was associated with a significantly increased risk of disease progression (pooled unadjusted hazard ratio: 1.43), while its relationship with overall survival remained inconclusive due to limited data. Despite methodological differences among studies, the findings suggest B7-H4 is overexpressed and potentially prognostic in ovarian cancer. Additional studies are required to validate its clinical utility in patient risk assessment and as a therapeutic target.

The treatment of patients with advanced epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) whose disease progresses after tyrosine-kinase inhibitors (TKIs) treatment has become a research hotspot.

To evaluate the diagnostic performance of PAX1 gene methylation in the detection of cervical lesions and assess its potential clinical application in cervical cancer screening through both a single-centre study and a meta-analysis.

Endometriosis-associated ovarian cancer (EAOC) mainly includes endometrioid ovarian cancer (ENOC) and clear cell ovarian cancer (CCOC). The Cancer Genome Atlas (TCGA) revealed four molecular subtypes of endometrial cancer (EC) in 2013, which have been proven pivotal in the diagnostic, prognostic and therapeutic domains of EC. Existing evidence indicates that EC and EAOC molecular analysis have similar significance. This review aims to investigate the distribution, staging and prognostic characteristics of molecular subtypes in EAOC.

This study aims to identify core genes closely associated with the diagnosis and prognosis of colorectal cancer (CRC) using transcriptome-based meta-analysis approach and machine learning algorithms. Nine CRC datasets from the GEO database were integrated for differential gene expression analysis and WGCNA to identify key genes. Ninety-six combinations of machine learning algorithms were employed to further refine the selection of core genes and validate their diagnostic performance. Functional enrichment, molecular pathways, and associations with the immune microenvironment of core genes were analyzed using GSEA, CIBERSORT, and ssGSEA. Drug sensitivity predictions were performed to evaluate the impact of core genes on CRC drug response, and molecular docking simulations were used to identify candidate compounds targeting the core genes. A total of 26 core genes were identified, among which the high expression of the SACS gene was significantly associated with poor prognosis, advanced stage, and specific pathological subtypes in CRC patients. GSEA revealed that high SACS expression prominently activates cell cycle regulatory pathways and immune pathways while suppressing metabolic pathways. Furthermore, in vitro experiments demonstrated that SACS is highly expressed in CRC cells and that its knockdown significantly inhibits CRC cell proliferation, suggesting its functional role in tumor growth. Immune analysis showed that high SACS expression was positively correlated with activated NK cells but negatively correlated with Tregs and resting NK cells. Drug sensitivity analysis indicated that high SACS expression reduces sensitivity to oxaliplatin. Molecular docking identified coumestrol and quercetin as potential compounds targeting SACS. SACS promotes CRC progression by regulating cell cycle pathways, the immune microenvironment, and metabolic pathways. And it may serve as a potential therapeutic target for CRC.

Glycolysis, a central process of cellular energy metabolism, has been shown to be closely associated with the development of hepatocellular carcinoma (HCC). This study aimed to investigate the prognostic value of the glycolysis gene set (GGS) in HCC.

Lung cancer remains a leading cause of global morbidity and mortality, imposing a significant healthcare burden worldwide. To comprehensively investigate potential risk factors for lung cancer and provide a theoretical basis for its prevention and treatment, we utilized publicly available genome-wide association study data of European ancestry. We treated various traits as exposures and lung cancer as the outcome. Causal relationships were assessed using 5 Mendelian randomization (MR) methods: inverse-variance weighted, constrained maximum likelihood and model averaging, debiased inverse-variance weighted, contamination mixture, and Mendelian randomization-robust adjusted profile score. We subsequently performed meta-analysis and median-based MR to synthesize the roles of different risk factors in lung cancer development. Following outlier removal via radial MR and MR analyses, we identified 88, 113, 248, and 232 exposure datasets showing causal associations with lung adenocarcinoma, small cell lung cancer, lung cancer overall, and squamous cell lung cancer, respectively. Further integration via meta-analysis and median MR revealed that higher educational attainment may reduce lung cancer risk by delaying age at first sexual intercourse, increasing age at first childbirth, lowering body mass index and adiposity, and reducing smoking frequency. Our comprehensive analysis suggests that education may play a protective role against lung carcinogenesis, potentially mediated through behavioral changes such as reduced smoking and modifications in physical health indicators including body mass index and adiposity.

Claudin 18.2 (CLDN18.2) is a novel treatment target for patients with unresectable or stage IV gastric cancer. However, it remains unclear whether the expression of CLDN18.2 affects survival outcomes. In total, 586 patients with GC were enrolled in this study. CLDN18.2 expression in cancer cells was analyzed by immunohistochemistry. Correlations between CLDN18.2 expression and several clinicopathological factors and survival outcomes were investigated. We also performed a systematic review and a meta-analysis. CLDN18.2 expression was mainly observed in the cell membrane. The CLDN18.2 expression was not significantly correlated with any clinicopathological factor. In all patients, CLDN18.2 did not significantly affect OS. In patients with the diffuse type, the overall survival of patients with CLDN18.2-high expression was worse than that of patients with CLDN18.2-low expression, although the difference was not significant (p = 0.092). Meta-analyses revealed that CLDN18.2 was not significant prognostic factor in resected cases, although CLDN18.2 negative cases showed a trend for worse survival. In, conclusion, CLDN18.2 was not a significant prognostic factor in general, although CLDN18.2 negative cases showed a trend for worse survival. We revealed that patients with CLDN18.2 high expression showed worse survival outcomes especially in the diffuse type.

Cancer cells harbor somatic mutations that generate novel amino acid sequences that are absent in the self-proteome. These mutation-derived cancer-specific peptides are defined as "neo-peptides". Neo-peptides eliciting immune responses, i.e. immunogenic neo-peptides, are defined as "neo-epitopes". Given their relevance to cancer immunotherapy, we conducted a meta-analysis to examine how experimental evidence informs our understanding of neo-epitopes. Our study is the largest reported to date. Using the cancer epitope database and analysis resource (CEDAR), we analyzed over 16,000 neo-peptides tested in more than 20,000 T cell assays across 180 studies. We found that validated neo-epitope frequencies varied across cancer types, with the highest rates in skin and lung and the lowest in colorectal cancer. Neo-epitopes were enriched in driver genes such as TP53 and KRAS. However, testing frequency correlated with mutation prevalence, revealing bias toward recurrent mutations. Despite the high sequence similarity among RAS family members, validated neo-epitope overlap was minimal, challenging pan-RAS strategies. Shared neo-epitopes across cancer types are rare, with only 16 validated in more than one cancer type. While most assays involved HLA class I, class II alleles presented a higher proportion of validated neo-epitopes. Specific alleles, including HLA-B*40:01 and HLA-DRB1*11:01, were enriched for neo-epitopes, whereas others, like HLA-A*02:01, were enriched for non-immunogenic neo-peptides. Finally, amino acid substitutions that altered hydrophobicity or charge were more common in neo-epitopes. Together, these findings define key features of neo-epitopes, expose methodological and biological biases in the literature, and highlight opportunities to improve the selection and prioritization of neo-epitopes for cancer immunotherapy.