ArticleNature communications2016
Rare disruptive mutations and their contribution to the heritable risk of colorectal cancer.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
107 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- UK clinical practice guidelines for the management of patients with constitutionalJournal of medical genetics · 2025Guideline
- Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2023Guideline
- A Systematic Literature Review of Whole Exome and Genome Sequencing Population Studies of Genetic Susceptibility to Cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2020Pooled it
- Validation of Recently Proposed Colorectal Cancer Susceptibility Gene Variants in an Analysis of Families and Patients-a Systematic Review.Gastroenterology · 2017Pooled it
- Pan-cancer multi-omics analysis reveals upregulation of the POLE2 subunit of DNA polymerase epsilon and its associations with patient survival and cellular pathways beyond DNA replication.NAR genomics and bioinformatics · 2026Article
- Effect of a polygenic risk score in patients with late-onset, early-onset, familial, or hereditary colorectal cancer.JNCI cancer spectrum · 2026Article
- Allogeneic hematopoietic stem cell transplantation in ERCC6L2 disease.Blood advances · 2026Article
- Mice carrying the homologous human shelterin POT1-L259S mutation linked to pulmonary fibrosis show a telomerase deficiency-like phenotype with telomere shortening with increasing mouse generations.Genes & development · 2025Article
- Tumour spectrum, distinguishing features and management recommendations for NTHL1-associated tumour syndrome: a systematic review.Hereditary cancer in clinical practice · 2025Review
- POT1 genetic testing in melanoma-prone families in Sweden: germline variant prevalence and tumor spectrum in identified carriers.Acta oncologica (Stockholm, Sweden) · 2025Article
- GermlineJCO precision oncology · 2025Article
- Active telomere elongation by a subclass of cancer-associated POT1 mutations.Genes & development · 2025Article
- To cleave or not and how? The DNA exonucleases and endonucleases in immunity.Genes & diseases · 2025Review
- Exon disruptive variants in Populus trichocarpa associated with wood properties exhibit distinct gene expression patterns.The plant genome · 2025Article
- Leveraging genome-wide association studies to better understand the etiology of cancers.Cancer science · 2025Review
- Telomeres, telomerase, and cancer: mechanisms, biomarkers, and therapeutics.Experimental hematology & oncology · 2025Review
- Prognosis and clinicopathological features of patients with early-onset and late-onset colorectal cancer with second primary malignancies.Journal of gastroenterology and hepatology · 2025Article
- Integrating next-generation sequencing and artificial intelligence for the identification and validation of pathogenic variants in colorectal cancer.Frontiers in oncology · 2025Article
- Integrated promoter-capture Hi-C and Hi-C analysis reveals fine-tuned regulation of the 3D chromatin architecture in colorectal cancer.Frontiers in genetics · 2025Article
- POLE2 silencing inhibits the progression of colorectal carcinoma cells via wnt signaling axis.Cancer biology & therapy · 2024Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
Abstract
Colorectal cancer (CRC) displays a complex pattern of inheritance. It is postulated that much of the missing heritability of CRC is enshrined in high-impact rare alleles, which are mechanistically and clinically important. In this study, we assay the impact of rare germline mutations on CRC, analysing high-coverage exome sequencing data on 1,006 early-onset familial CRC cases and 1,609 healthy controls, with additional sequencing and array data on up to 5,552 cases and 6,792 controls. We identify highly penetrant rare mutations in 16% of familial CRC. Although the majority of these reside in known genes, we identify POT1, POLE2 and MRE11 as candidate CRC genes. We did not identify any coding low-frequency alleles (1-5%) with moderate effect. Our study clarifies the genetic architecture of CRC and probably discounts the existence of further major high-penetrance susceptibility genes, which individually account for >1% of the familial risk. Our results inform future study design and provide a resource for contextualizing the impact of new CRC genes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.