Colorectal cancer (CRC) continues to be a common health condition and one of the most prevalent and lethal  cancers worldwide. CRC is the third most leading cancer by incidence and second most common cause of cancer mortality. Emerging evidence showing that inherited genetic variants in genes coding for DNA repair enzymes have potential role in increasing the risk of CRC. Among these,  polymorphisms in the XRCC1 has been widely investigated, although the results have been varied in different populations.

Aberrant mucin expression is implicated in lower gastrointestinal tract (GIT) cancers, yet its clinicopathological relevance remains poorly understood. To identify distinct mucin signatures in association with (pre)tumour subtypes, anatomical location, and clinical outcomes, we conducted a systematic review and meta-analysis of MEDLINE articles published between January 2001 and September 2025. Studies were included if they assessed mucin expression in lower GIT (pre)malignant lesions. Fifty-eight studies were eligible. MUC2 and MUC5AC expression was upregulated in serrated polyps and mucinous- and microsatellite instability (MSI)-associated proximal adenocarcinomas, whereas a downregulation of MUC2 was noted in advanced adenomas and non-mucinous distal tumours. Discrepancies in survival in relation to high-level or low-level MUC2 further suggested that this glycoprotein cooperates with other mucins during carcinogenesis. Notably, abundant MUC1 expression was seen in adenomas with high-grade dysplasia and together with high-level MUC13 correlated with (non-)mucinous CRC types and poor prognosis. Similar mucin signatures were also found in small intestinal adenocarcinoma, yet MUC2 was downregulated and increased MUC5AC rather associated with a worse survival, emphasizing the role of tumour location in influencing tumour behaviour. In conclusion, aberrant mucin signatures reflect distinct molecular pathways in (pre)malignant GIT lesions and highlight their potential utility as biomarkers and therapeutic targets. Schematic representation of the main findings regarding altered mucin signalling in several precancerous lesions (adenomatous (i.e., conventional pathway 1) and serrated polyps (i.e. pathway 2)) and small intestinal (SIA) and colorectal (CRC) adenocarcinomas and its clinicopathological significance (outcome, anatomical location (proximal/distal), molecular subtypes (MSI, (non)-mucinous).

Solute Carrier Family 7 Member 11 (SLC7A11), a redox homeostasis and metabolism regulator, is frequently overexpressed and mutated in cancers, contributing to progression and therapy resistance. This study systematically reviewed and meta-analyzed its prognostic value, mutational landscape, role in resistance, and its therapeutic potential. A comprehensive search (2010-2024) across PubMed and ScienceDirect identified 236 studies, alongside TCGA data from 30 cancer types and 128 mutations from GDC. Prognostic and clinicopathological correlations were assessed using hazard ratios (HRs), with fixed/random effects models based on heterogeneity (I2), and significance tested via Z-tests (p < 0.05). Publication bias was evaluated using Begg's and Egger's tests. General linear models explored associations with resistance and pathway alterations. Interestingly, SLC7A11 overexpression was associated with poor prognosis (HR = 1.22), adverse clinicopathological features viz. TNM-stage and therapy resistance like chemoresistance (p < 0.001). Mutation analysis revealed diverse alterations and frequent heterozygous deletions, prevalently, missense mutation underscoring its oncogenic role. Moreover, SLC7A11 inhibitors, particularly sulfasalazine and erastin, effectively reversed resistance, in 18 clinical trials (Phase I-III) completed over the last decade. Targeting SLC7A11 presents a promising therapeutic strategy to modulate redox balance, metabolism, and ferroptosis, towards efficient cancer treatments.

Muir-Torre syndrome (MTS) is a hereditary tumor predisposition syndrome associated with sebaceous neoplasms. Immunohistochemistry (IHC) for loss of mismatch repair (MMR) proteins in these tumors is used as a screening test, but its diagnostic accuracy has not been rigorously assessed.

The signal transducer and activator of transcription 5 (STAT5) proteins, STAT5A and STAT5B, are highly homologous transcription factors with distinct roles in cancer biology. While STAT5A has been characterized as a context-dependent modulator of tumor progression, the prognostic significance of STAT5B remains less clear. Here, we conducted a systematic meta-analysis of STAT5B to evaluate its association with overall survival across cancers and to compare its prognostic role with that of STAT5A, as reported previously.

BRAF mutations are found in 10% of colon cancers (CCs) and are associated with poor prognosis in metastatic disease. BRAF V600E predicts sensitivity to cetuximab + encorafenib in the metastatic setting. With new trials testing encorafenib-containing regimens for early-stage CC, we sought to characterize the clinical outcomes of early-stage BRAF V600E CC.

DNA promoter methylation is one of the main epigenetic mechanisms of silencing of tumor-suppressor genes in cancer. Accumulating scientific evidence has shown various genes with aberrant DNA methylation in oral cancer (OC), however, the magnitude of the association between DNA methylation and OC risk remains controversial.

The T allele variant of TERT rs2736098 has been associated with an increased risk of lung cancer (LC), yet various studies have yielded inconsistent findings. The purpose of this study is to verify the association between the rs2736098 variant and LC risk, as well as to investigate the differences in this association across different ethnic groups (Caucasians and Asians), various LC subtypes, and distinct smoking statuses. A computer search was conducted for literatures published up to December 20, 2024, in PubMed, Embase, Web of Science, and MEDLINE databases. Data were analyzed using RevMan 5.3, while sensitivity analysis and publication bias were assessed using Stata 14.0. The stability of the results was evaluated with TSA software Registration number: CRD420251030755. The T allele variant of rs2736098 was associated with an increased risk of LC ([OR] = 1.22, 95%CI [1.18, 1.27]), and this association was observed in both Caucasians ([OR] = 1.17, 95%CI [1.14, 1.20]) and Asians ([OR] = 1.26, 95%CI [1.19, 1.34]), with a stronger association in Asians than in Caucasians (Subgroup differences: P = 0.03, I2 = 79.7%). In specific LC subtypes, rs2736098[T] was linked to the risk of NSCLC and LUAD in both Caucasians and Asians (P < 0.05), and the strength of the association with NSCLC and LUAD was greater in Asians than in Caucasians (Subgroup differences: P < 0.05, I2 > 50%). Additionally, rs2736098[T] was associated with the risk of SCLC and LUSC in Asians (P < 0.05), with a similar strength of association for NSCLC and SCLC (subgroup differences: P = 0.87, I2 = 0%), but a stronger association for LUAD than for LUSC (subgroup differences: P = 0.01, I2 = 84.7%). The rs2736098[T] variant was also associated with the risk of LC in both Caucasian smokers/non-smokers and Asian smokers/non-smokers (P < 0.05), and the strength of the association did not vary between Caucasian smokers/non-smokers and Asian smokers/non-smokers (P ≥ 0.05, Subgroup differences: I2 < 50%). Within LC subtypes, rs2736098[T] was primarily associated with the risk of NSCLC in Asian smokers ([OR] = 1.59, 95%CI[1.19, 2.12]) and the risk of LUAD in Asian non-smokers ([OR] = 1.43, 95%CI[1.17, 1.75]). The T allele variant of rs2736098 is associated with LC risk, and Asians have a higher risk of LC, NSCLC and LUAD due to the rs2736098 variant compared to Caucasians. Therefore, there is a difference in the strength of the association between the two populations for LC risk due to the rs2736098 variant. Additionally, regardless of whether Caucasians or Asians are smokers, they are likely to be at risk for LC due to the variant in rs2736098.

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.

Urinary bladder cancer (UBC), the tenth most common globally with a male predominance, has its risk factors like smoking and single nucleotide polymorphisms (SNPs), yet the MYC gene's role, especially the rs9642880 GT/TT polymorphism on chromosome 8q24.21, in cancer susceptibility is underexplored.

Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for minimal residual disease (MRD) detection and recurrence risk stratification in colorectal cancer (CRC). However, its prognostic significance in stage III CRC remains incompletely defined. This meta-analysis aimed to evaluate the association between postoperative ctDNA positivity and recurrence risk in patients with stage III CRC.

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.

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.

We synthesized the evidence on the accuracy of Deep learning in detecting colorectal cancer microsatellite instability to contribute to the development and updating of intelligent detection tools.

Sebaceous neoplasms are rare skin tumours linked with Lynch syndrome (LS), particularly the Muir-Torre syndrome (MTS) variant. They present an opportunity for early LS detection due to their association with mismatch repair (MMR) gene pathogenic variants. This study aims to provide an accurate estimate of LS prevalence among patients with sebaceous adenomas and carcinomas. We performed a systematic review and meta-analysis of studies published between 2005 and 2024. Eligible studies utilised germline testing for MMR mutations. The studies were stratified by diagnostic approach and analysed using proportional meta-analysis to determine LS prevalence. Subgroup analyses were conducted by population characteristics and diagnostic criteria. Lynch Syndrome prevalence among patients with sebaceous neoplasms varied across the 9 studies that met eligibility criteria, ranging from 0.8% to 29.0%. LS among patients with sebaceous carcinomas was 6.6% (95% CI: 3.6%-9.5%). Population-based studies had a higher LS identification rate (10.6%), while multi-centre and single-centre studies reported lower rates. Studies using a history suggestive of MTS or MMR-deficient tumours as criteria showed the highest LS prevalence. Male patients had higher sebaceous neoplasms prevalence, with LS-positive cases presenting at a younger age than typical sporadic cases. Our findings highlight the potential for LS detection in patients with sebaceous neoplasms, particularly those with MMR deficiency or a suggestive MTS history. Increased testing in this group could facilitate early LS detection, improving outcomes through screening and preventive strategies. Universal MMR testing for sebaceous tumours warrants consideration as a strategy to capture at-risk LS patients.

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.

Consensus molecular subtypes (CMSs) of metastatic colorectal cancer (mCRC) are debatable biomarkers. An individual patient data (IPD) meta-analysis was performed to test for impact on objective response rates (ORRs), progression-free survival (PFS) and overall survival (OS), and treatment interaction.

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.

Urinary cell-free DNA (ucfDNA) offers a noninvasive approach for cancer detection, but its diagnostic utility in non-urothelial cancers remains unclear. We systematically evaluated the diagnostic and prognostic value of ucfDNA for these cancers and compared its performance with other liquid biopsies through network meta-analysis.