ArticlePLoS genetics2016
Identification of Novel Candidate Genes for Early-Onset Colorectal Cancer Susceptibility.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 3 of them syntheses that pooled it.
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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.
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Who cites it
38 citing papers in PubMed, 3 syntheses or guidelines pooled it, 62 citations in OpenAlex.
- 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
- Pooled it
- Validation of Recently Proposed Colorectal Cancer Susceptibility Gene Variants in an Analysis of Families and Patients-a Systematic Review.Gastroenterology · 2017Pooled it
- Closing the Diagnostic Gap in Early-Onset Colorectal Cancer: Red-Flag Symptoms, Screening, and Inherited Risk.Cancers · 2026Review
- Gene, genetics and genetic medicines in gastroenterology: Current status and its future.World journal of gastroenterology · 2026Review
- PTPN12 is a novel biomarker associated with genomic instability, therapeutic potentials, and immunomodulator in colorectal cancer.Frontiers in pharmacology · 2026Article
- Exome-based cancer predisposition gene testing can provide a genetic diagnosis for individuals with heterogeneous tumor phenotypes.European journal of human genetics : EJHG · 2025Article
- Germline Sequencing of Familial and Sporadic Early-Onset Colorectal Cancer: A Novel Pattern of Genes.International journal of molecular sciences · 2025Article
- Review
- Article
- Zinc Finger Protein 90 Knockdown Promotes Cisplatin Sensitivity via Nrf2/HO-1 Pathway in Ovarian Cancer Cell.Cancers · 2023Article
- The Relationship between LRP6 and Wnt/β-Catenin Pathway in Colorectal and Esophageal Cancer.Life (Basel, Switzerland) · 2023Article
- Transthyretin-induced increase in circ_0007411 represses neovascularization of human retinal microvascular endothelial cells in hyperglycemia via the miR-548m/PTPN12/SKP1/EGFR pathway.Annals of translational medicine · 2022Article
- Downregulation of secreted frizzled-related protein 4 inhibits hypoxia/reoxygenation injury in diabetic cardiomyocytes by protein tyrosine phosphatase nonreceptor type 12.Bioengineered · 2022Article
- Exploring the Wnt Pathway as a Therapeutic Target for Prostate Cancer.Biomolecules · 2022Review
- Review
- Hereditable variants of classical protein tyrosine phosphatase genes: Will they prove innocent or guilty?Frontiers in cell and developmental biology · 2022Review
- Exome sequencing of early-onset patients supports genetic heterogeneity in colorectal cancer.Scientific reports · 2021Article
- Analysis of genomic pathogenesis according to the revised Bethesda guidelines and additional criteria.Journal of cancer research and clinical oncology · 2021Article
- Regulation of Wnt Signaling Pathways at the Plasma Membrane and Their Misregulation in Cancer.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Approximately 25-30% of colorectal cancer (CRC) cases are expected to result from a genetic predisposition, but in only 5-10% of these cases highly penetrant germline mutations are found. The remaining CRC heritability is still unexplained, and may be caused by a hitherto-undefined set of rare variants with a moderately penetrant risk. Here we aimed to identify novel risk factors for early-onset CRC using whole-exome sequencing, which was performed on a cohort of CRC individuals (n = 55) with a disease onset before 45 years of age. We searched for genes that were recurrently affected by rare variants (minor allele frequency ≤ 0.001) with potentially damaging effects and, subsequently, re-sequenced the candidate genes in a replication cohort of 174 early-onset or familial CRC individuals. Two functionally relevant genes with low frequency variants with potentially damaging effects, PTPN12 and LRP6, were found in at least three individuals. The protein tyrosine phosphatase PTP-PEST, encoded by PTPN12, is a regulator of cell motility and LRP6 is a component of the WNT-FZD-LRP5-LRP6 complex that triggers WNT signaling. All variants in LRP6 were identified in individuals with an extremely early-onset of the disease (≤30 years of age), and two of the three variants showed increased WNT signaling activity in vitro. In conclusion, we present PTPN12 and LRP6 as novel candidates contributing to the heterogeneous susceptibility to CRC.
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