SynthesisAnnals of oncology : official journal of the European Society for Medical Oncology2024
Genome-wide association studies and Mendelian randomization analyses provide insights into the causes of early-onset colorectal cancer.
Synthesis in Annals of oncology : official journal of the European Society for Medical Oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Causal effect of thyroid cancer on secondary primary malignancies: findings from the UK Biobank and FinnGen cohorts.Frontiers in immunology · 2024Pooled it
- Shaping the future of early-onset colorectal cancer prevention.Nature reviews. Cancer · 2026Review
- Closing the Diagnostic Gap in Early-Onset Colorectal Cancer: Red-Flag Symptoms, Screening, and Inherited Risk.Cancers · 2026Review
- Early-onset gastrointestinal cancer patterns in Navarre: incidence, tumour features and patient survival outcomes.ESMO real world data and digital oncology · 2026Article
- Telmisartan Repurposing Targets Novel Biomarkers for Precision Colorectal Cancer Therapy.Pharmaceutics · 2026Article
- A Neuro-Immune Score Defines a Stromal-Neural and Immune-Segregated Microenvironment Associated with Poor Prognosis in Colorectal Cancer.International journal of molecular sciences · 2026Article
- Metabolic and Laboratory Biomarkers in Early-Onset Versus Late-Onset Colorectal Cancer: A Case-Control Study.Cancers · 2026Article
- Early-onset cancer and modifiable risk: quantifying the combined impact of excess body weight and alcohol on breast and colorectal cancer in Italy (18-34 years).BMC public health · 2026Article
- Review
- Lynch Syndrome: An Update of Underlying Molecular Mechanisms, Phenotypes and Methods to Classify Variants of Uncertain Significance.Biomedicines · 2026Review
- Upregulation of Hsa_circ_0077007 Expression is Used for Prognosis and Targeted Therapy of Colorectal Cancer.Biochemical genetics · 2026Article
- Accelerating discovery of cancer causes for prevention in the era of rising early-onset cancers.Cell · 2026Review
- Diabetogenic processes for insulin resistance-linked hyperinsulinaemia are associated with colorectal cancer.Diabetologia · 2026Article
- Alcohol use disorder: an Australian perspective on screening, diagnosis, treatment and prevention.Internal medicine journal · 2026Review
- Increase of early-onset colorectal cancer: a cohort effect.Journal of the National Cancer Institute · 2026Article
- Risk assessment of secondary primary malignancies: results from two large prospective European cohorts.NPJ precision oncology · 2026Article
- Clusters of Anthropometric Features in Colorectal Cancer Patients with Synchronous Metastases and Their Association with Overall Survival and RAS Mutation.Journal of gastrointestinal cancer · 2026Article
- Why Is Colorectal Cancer Occurring Earlier? Metabolic Dysfunction, Underrecognized Carcinogens, and Emerging Controversies.Current obesity reports · 2026Review
- Definition of Sporadic Early-Onset Invasive Solid Organ Cancers in Adults.Oncology and therapy · 2026Article
- A prospective investigation of early-onset colorectal cancer risk factors-pooled analysis of three large-scale European cohorts.British journal of cancer · 2026Article
Corrections and comments
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Authors and funding
37 authors.
Funding
Abstract
backgroundThe incidence of early-onset colorectal cancer (EOCRC; diagnosed <50 years of age) is rising globally; however, the causes underlying this trend are largely unknown. CRC has strong genetic and environmental determinants, yet common genetic variants and causal modifiable risk factors underlying EOCRC are unknown. We conducted the first EOCRC-specific genome-wide association study (GWAS) and Mendelian randomization (MR) analyses to explore germline genetic and causal modifiable risk factors associated with EOCRC. PATIENTS AND
methodsWe conducted a GWAS meta-analysis of 6176 EOCRC cases and 65 829 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT), the Colon Cancer Family Registry (CCFR), and the UK Biobank. We then used the EOCRC GWAS to investigate 28 modifiable risk factors using two-sample MR.
resultsWe found two novel risk loci for EOCRC at 1p34.1 and 4p15.33, which were not previously associated with CRC risk. We identified a deleterious coding variant (rs36053993, G396D) at polyposis-associated DNA repair gene MUTYH (odds ratio 1.80, 95% confidence interval 1.47-2.22) but show that most of the common genetic susceptibility was from noncoding signals enriched in epigenetic markers present in gastrointestinal tract cells. We identified new EOCRC-susceptibility genes, and in addition to pathways such as transforming growth factor (TGF) β, suppressor of Mothers Against Decapentaplegic (SMAD), bone morphogenetic protein (BMP) and phosphatidylinositol kinase (PI3K) signaling, our study highlights a role for insulin signaling and immune/infection-related pathways in EOCRC. In our MR analyses, we found novel evidence of probable causal associations for higher levels of body size and metabolic factors-such as body fat percentage, waist circumference, waist-to-hip ratio, basal metabolic rate, and fasting insulin-higher alcohol drinking, and lower education attainment with increased EOCRC risk.
conclusionsOur novel findings indicate inherited susceptibility to EOCRC and suggest modifiable lifestyle and metabolic targets that could also be used to risk-stratify individuals for personalized screening strategies or other interventions.
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