Background: Germline alleles near genes encoding certain immune checkpoints (CTLA4, CD200) are associated with autoimmune/autoinflammatory disease and cancer, but in opposite ways. This motivates a systematic search for additional germline alleles with this pattern with the aim of identifying potential cancer immunotherapeutic targets using human genetics. Methods: Pairwise fixed effect cross-disorder meta-analyses combining genome-wide association studies (GWAS) for breast, prostate, ovarian and endometrial cancers (240,540 cases/317,000 controls) and seven autoimmune/autoinflammatory diseases (112,631 cases/895,386 controls) coupled with in silico follow-up. Results: Meta-analyses followed by linkage disequilibrium clumping identified 312 unique, independent lead variants with p < 5 × 10-8 associated with at least one of the cancer types at p < 10-3 and one of the autoimmune/autoinflammatory diseases at p < 10-3. At each lead variant, the allele that conferred autoimmune/autoinflammatory disease risk was protective for cancer. Mapping led variants to nearest genes as putative functional targets and focusing on immune-related genes implicated 32 genes. Tumor bulk RNA-Seq data highlighted that the tumor expression of 5/32 genes (IRF1, IKZF1, SPI1, SH2B3, LAT) was each strongly correlated (Spearman's ρ > 0.5) with at least one intra-tumor T/myeloid cell infiltration marker (CD4, CD8A, CD11B, CD45) in every one of the cancer types. Tumor single-cell RNA-Seq data from all cancer types showed that the five genes were more likely to be expressed in intra-tumor immune versus malignant cells. The five lead SNPs corresponding to these genes were linked to them via the expression of quantitative trait locus mechanisms and at least one additional line of functional evidence. Proteins encoded by the genes were predicted to be druggable. Conclusions: We provide population-scale germline genetic and functional genomic evidence to support further evaluation of the proteins encoded by IRF1, IKZF1, SPI1, SH2B3 and LAT as possible targets for cancer immunotherapy.

Postoperative adjuvant epidermal growth factor receptor (EGFR) inhibitor osimertinib is the standard care for stage IB-IIIB non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R mutation, following complete tumour resection, with or without prior platinum-based adjuvant chemotherapy. However, the role of EGFR tyrosine kinase inhibitors (TKIs) in this setting is debated, particularly concerning long-term curative effects versus recurrence delay. Uncertainties persist around treatment duration, harms, and effectiveness across disease stages, prior chemotherapy, or EGFR-sensitising mutation types.

Background: Colorectal cancer (CRC) is a significant cause of cancer-related mortality worldwide. While many health examination indicators might be associated with CRC, their causal relationships remain unclear. The authors analyzed their causal relationship in European and East Asian populations. Methods: The authors collected the genome-wide association data for 33 clinical indicators and CRC in European and East Asian populations from the IEU OpenGWAS project and Riken's Japanese Genetic Association Database. These indicators include 13 hematological indicators, 7 liver function indicators, 2 kidney function indicators, 5 lipid metabolism indicators, 2 glucose metabolism indicators, 1 electrolyte indicator, and 3 comorbidity indicators. The authors performed univariate (UV) and multivariate (MV) Mendelian randomization (MR) analyses on the European and East Asian populations and followed a meta-analysis. Results: UVMR analysis identified 11 indicators (white blood cell count [WBC], mean corpuscular hemoglobin [MCH], mean corpuscular hemoglobin concentration, mean corpuscular volume [MCV], platelet count [Plt], C-reactive protein [CRP], total protein [TP], aspartate aminotransferase [AST], total cholesterol [TC], low-density lipoprotein cholesterol, and apolipoprotein B) with significant causal relationships (p < 0.05). Notably, AST, TC, glycated hemoglobin, and serum creatinine showed inverted causal relationships in different populations. After MV adjustment for TC and TP, MCH (odds ratio [OR]EU = 1.0012, 1.0000 to 1.0024; ORmeta = 1.0012, 1.0001 to 1.0024), Plt (OREU = 0.9986, 0.9974 to 0.9998; ORmeta = 0.9986, 0.9974 to 0.9998), and CRP (OREU = 0.9981, 0.9965 to 0.9998; ORmeta = 0.9981, 0.9965 to 0.9998) were independent influencing indicators in European and Eurasian populations, whereas WBC (OREAS = 0.8316, 0.7005 to 0.9871), MCH (OREAS = 1.2430, 1.1132 to 1.3879), and MCV (OREAS = 1.0012, 1.0001 to 1.0024) were independent influencing indicators in the East Asian population. Conclusion: The causal relationship between MCH, TP, and Plt and CRC has been discovered for the first time. Furthermore, TC and CRP were also independent influencing indicators. These findings offer beneficial referential value for the enhancement of preliminary screening protocols for CRC.

Recent studies suggest a link between air pollution and lung cancer, but causality remains uncertain due to confounding and reverse causation. Mendelian randomization (MR) reduces such bias and offers a new way to explore this relationship. MR is a method that uses genetic variants as instrumental variables to assess the causal relationship between an exposure and an outcome, effectively controlling for confounding and reverse causation. The inverse-variance weighted method is a commonly used approach in MR analysis, which estimates the overall causal effect by weighting the effect ratios of multiple single nucleotide polymorphisms, assuming all instruments are valid. Based on 2-sample MR, this study incorporated 5 air pollution indices and conducted MR analyses with lung cancer outcome data from 2 different sources. Subsequently, a meta-analysis was performed on the primary inverse-variance weighted results, followed by multiple corrections of the thresholds after the meta-analysis to ensure accuracy. Finally, reverse causality was tested through MR analysis for air pollution indices significantly associated with lung cancer. And the selection criteria for instrumental variables were: P < 5 × 10⁻⁶, F > 10, minor allele frequency > 0.01, clump_kb = 10,000, and clump_r2 = 0.001. Five air pollution indices were analyzed using MR analysis and meta-analysis with lung cancer data from the FinnGen R12 and OpenGWAS databases. Multiple corrections were applied to the significance threshold results after the meta-analysis. The final results showed that only nitrogen dioxide (NO₂) exhibited a significant association, with an OR of 3.426 (95% CI: 1.897-6.186, P = 2.21 × 10⁻⁴). Additionally, the positive air pollution index NO₂ showed no evidence of reverse causality with lung cancer from either data source. This study demonstrates a significant causal association between NO₂ and lung cancer, indicating that NO₂ may be a potential risk factor for lung cancer.

Acute myeloid leukemia (AML) with core-binding factor alterations (CBF-AML) is a notable subtype characterized by specific genetic alterations and a relatively favorable prognosis. Despite this, a significant proportion of CBF-AML patients experience relapse, indicating the potential prognostic role of other co-present cytogenetic abnormalities and gene mutations.

Early detection of pancreatic cancer is essential for improving survival rates. However, noninvasive diagnostic methods are lacking. Novel biomarkers, detectable through liquid biopsy, such as circulating tumor DNA (ctDNA), microRNAs (miRNAs), protein markers, and metabolites, hold promise for early diagnosis.

Pathogenic variants (PVs) of BRCA1 and BRCA2 predispose individuals to a higher risk of breast and ovarian cancer; however, the precise risks posed by other cancer susceptibility genes remain unclear, particularly in Asian populations.

Somatic USP8 variants are common in corticotroph tumours, but their reported prevalence and association with clinical characteristics vary widely among publications.

This meta-analysis aimed to clarify the connection between six polymorphisms in the FTO gene and susceptibility to cancer.

In recent years, artificial intelligence (AI) tools have become widely studied for thyroid ultrasonography (USG) classification. The real-world applicability of these developed tools as pre-operative diagnostic aids is limited due to model overfitting, clinician trust, and a lack of gold standard surgical histology as ground truth class label. The ongoing dilemma within clinical thyroidology is surgical decision making for indeterminate thyroid nodules (ITN). Genomic sequencing classifiers (GSC) have been utilised for this purpose; however, costs and availability preclude universal adoption creating an inequity gap. We conducted this review to analyse the current evidence of AI in ITN diagnosis without the use of GSC.

This investigation evaluates the clinical significance and molecular mechanisms of microRNA-486 (miR-486) as a potential biomarker in non-small cell lung cancer (NSCLC) through an integrative analytical approach.

Venetoclax with hypomethylating agents (VEN-HMAs) has shown inconsistent efficacy versus induction chemotherapy (IC) in newly diagnosed AML (ND-AML). Whether or not VEN-HMAs are of clinical benefit remains uncertain. We conducted this meta-analysis to evaluate the clinical benefit of VEN-HMAs versus IC in various subtypes of ND-AML.

The aim of this systematic review and meta-analysis was to describe the perinatal outcomes and modifiers of antenatally diagnosed cystic hygroma (CH).

Several single nucleotide polymorphisms (SNPs) identified through genome-wide association studies (GWASs) on colorectal cancer (CRC) incidence are also shown as promising predictors of clinical outcomes in CRC patients. These genetic variants might help inform precision prognostic strategies by predicting disease progression, treatment response, and overall survival, thereby guiding more personalized treatment plans. However, conflicting evidence exists regarding their clinical relevance.

Immunotherapy has become the first-line treatment for metastatic mismatch repair deficient (dMMR) colorectal cancer. The efficacy and safety of neoadjuvant immunotherapy for the treatment of non-metastatic dMMR colorectal cancer remain unclear. In this article, we explore the clinical effect and safety of neoadjuvant immunotherapy for non-metastatic dMMR colorectal cancer.

We conducted a systematic review and meta-analysis to evaluate the performance of magnetic resonance imaging (MRI)-derived deep learning (DL) models in predicting 1p/19q codeletion status in glioma patients.

Microsatellite instability (MSI) is a novel predictive biomarker for chemotherapy and immunotherapy response, as well as prognostic indicator in colorectal cancer (CRC). The current standard for MSI identification is polymerase chain reaction (PCR) testing or the immunohistochemical analysis of tumor biopsy samples. However, tumor heterogeneity and procedure complications pose challenges to these techniques. CT and MRI-based radiomics models offer a promising non-invasive approach for this purpose.

While there is a growing volume of evidence suggesting that relatively prevalent functional polymorphisms present within apoptosis-related genes may influence human prostate cancer (PCa) susceptibility, the clinical relevance of these findings remains inconclusive.

Aberrations in the regulatory genome play a pivotal role in population-level disease predisposition. Annotation of the regulatory regions using appropriate primary tissues - instead of cell lines affected by selection and other confounding factors - could shed new light into mechanisms underlying common conditions. We test this approach in uterine leiomyomas, highly prevalent benign neoplasms of the myometrium, by creating 15-state chromatin annotations for myometrium and uterine leiomyomas. Integration with RNA-seq, ATAC-seq, HiChIP and methylation data enables us to compare the epigenomes of myometrium and ULs with distinct driver mutations, highlighting the role of bivalent regions in the neoplastic process. Subsequently, a genome wide association study meta-analysis is performed, using three different cohorts. Disease association loci are enriched at active chromatin, especially at enhancers, and harbor tumor- and driver mutation-specific chromatin states. At SATB2 locus we show the effect of the risk genotype already in the normal tissue. Integration of genome-wide association studies and deep regulatory genomics data from the correct tissue type represents a powerful approach in understanding population-level disease predisposition.

In the last twenty years, epidemiological research has suggested a potential decreased susceptibility to cancer among individuals diagnosed with Parkinson's disease (PD), although conflicting findings exist regarding the connection between PD and Colorectal cancer (CRC). This systematic review and meta-analysis were conducted to investigate the contemporary epidemiological data on the risk of CRC in PD.