ArticleGastroenterology2011
Variants in the netrin-1 receptor UNC5C prevent apoptosis and increase risk of familial colorectal cancer.
Article in Gastroenterology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 36 citations in OpenAlex.
- Identification of colorectal cancer molecular subtypes and prognostic features based on basement membrane-related genes.Journal of applied genetics · 2026Article
- The UNC5C T835M mutation associated with Alzheimer's disease leads to neurodegeneration involving oxidative stress and hippocampal atrophy in aged mice.Molecular neurodegeneration · 2025Article
- Research progress of the netrins and their receptors in cancer.Journal of cellular and molecular medicine · 2024Review
- Identification of a basement membrane-related gene signature for predicting prognosis, immune infiltration, and drug sensitivity in colorectal cancer.Frontiers in oncology · 2024Article
- Promoter methylation-mediated repression of UNC5 receptors and the associated clinical significance in human colorectal cancer.Clinical epigenetics · 2021Article
- Dominantly Inherited Hereditary Nonpolyposis Colorectal Cancer Not Caused by MMR Genes.Journal of clinical medicine · 2020Review
- Epigallocatechin gallate inhibits dimethylhydrazine-induced colorectal cancer in rats.World journal of gastroenterology · 2020Article
- UNC5C‑knockdown enhances the growth and metastasis of breast cancer cells by potentiating the integrin α6/β4 signaling pathway.International journal of oncology · 2020Article
- Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.Cell death and differentiation · 2018Review
- The Impact of UNC5C Genetic Variations on Neuroimaging in Alzheimer's Disease.Molecular neurobiology · 2016Article
- Article
- Epidermal Growth Factor Receptor-Dependent Mutual Amplification between Netrin-1 and the Hepatitis C Virus.PLoS biology · 2016Article
- Scarce evidence of the causal role of germline mutations in UNC5C in hereditary colorectal cancer and polyposis.Scientific reports · 2016Article
- Whole-exome sequencing of muscle-invasive bladder cancer identifies recurrent mutations of UNC5C and prognostic importance of DNA repair gene mutations on survival.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Article
- Genetic predisposition to colorectal cancer: where we stand and future perspectives.World journal of gastroenterology · 2014Review
- Evaluation of the colorectal cancer risk conferred by rare UNC5C alleles.World journal of gastroenterology · 2014Article
- Netrin-1 expression is an independent prognostic factor for poor patient survival in brain metastases.PloS one · 2014Article
- Dependence receptor TrkC is a putative colon cancer tumor suppressor.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
Corrections and comments
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Authors and funding
20 authors at 8 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsExpression of the netrin-1 dependence receptor UNC5C is reduced in many colorectal tumors; mice with the UNC5C mutations have increased progression of intestinal tumors. We investigated whether specific variants in UNC5C increase risk of colorectal cancer (CRC).
methodsWe analyzed the sequence of UNC5C in blood samples from 1801 patients with CRC and 4152 controls from 3 cohorts (France, United States, and Finland). Almost all cases from France and the United States had familial CRC; of the Finnish cases, 92 of 984 were familial. We analyzed whether CRC segregates with the UNC5C variant A628K in 3 families with histories of CRC. We also performed haplotype analysis to determine the origin of this variant.
resultsOf 817 patients with familial CRC, 14 had 1 of 4 different, unreported missense variants in UNC5C. The variants p.Asp353Asn (encodes D353N), p.Arg603Cys (encodes R603C), and p.Gln630Glu (encodes Q630E) did not occur significantly more often in cases than controls. The variant p.Ala628Lys (A628K) was detected in 3 families in the French cohort (odds ratio, 8.8; Wald's 95% confidence interval, 1.47-52.93; P = .03) and in 2 families in the US cohort (odds ratio, 1.9; P = .6) but was not detected in the Finnish cohort; UNC5C A628K segregated with CRC in families. Three families with A628K had a 109-kilobase identical haplotype that spanned most of UNC5C, indicating recent origin of this variant in white subjects (14 generations; 95% confidence interval, 6-36 generations). Transfection of HEK293T cells with UNC5C-A628K significantly reduced apoptosis compared with wild-type UNC5C, measured in an assay of active caspase-3.
conclusionsInherited mutations in UNC5C prevent apoptosis and increase risk of CRC.
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