ArticleGut2002
Explaining variation in familial adenomatous polyposis: relationship between genotype and phenotype and evidence for modifier genes.
Article in Gut, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 88 citations in OpenAlex.
- Challenges in developing and implementing international best practice guidance for intermediate-risk variants in cancer susceptibility genes:Journal of medical genetics · 2024Article
- First Evidence of Familial Transmission of Hereditary Gastrointestinal Polyposis Associated with GermlineVeterinary sciences · 2023Article
- Wild-type APC Influences the Severity of Familial Adenomatous Polyposis.Cellular and molecular gastroenterology and hepatology · 2022Article
- Linking stemness with colorectal cancer initiation, progression, and therapy.World journal of stem cells · 2019Review
- Elevated expression of p53 in early colon polyps in a pig model of human familial adenomatous polyposis.Journal of applied genetics · 2018Article
- Adenocarcinoma at the Ileostomy Site After a Proctocolectomy for Ulcerative Colitis and/or Familial Adenomatous Polyposis: An Overview.Ostomy/wound management · 2018Review
- CD36 - a plausible modifier of disease phenotype in familial adenomatous polyposis.Hereditary cancer in clinical practice · 2018Article
- Porcine familial adenomatous polyposis model enables systematic analysis of early events in adenoma progression.Scientific reports · 2017Article
- The genetic basis of colonic adenomatous polyposis syndromes.Hereditary cancer in clinical practice · 2017Review
- Colorectal cancer risk variants at 8q23.3 and 11q23.1 are associated with disease phenotype in APC mutation carriers.Familial cancer · 2016Article
- Segmental resection with primary anastomosis is not always safe in splenic flexure perforation.BMC research notes · 2016Article
- Genetic dissection of the Mom5 modifier locus and evaluation of Mom5 candidate genes.Mammalian genome : official journal of the International Mammalian Genome Society · 2015Article
- Common colorectal cancer risk alleles contribute to the multiple colorectal adenoma phenotype, but do not influence colonic polyposis in FAP.European journal of human genetics : EJHG · 2015Article
- Two Chinese pedigrees for adenomatous polyposis coli: new mutations at codon 1309 and predisposition to phenotypic variations.Familial cancer · 2014Article
- The importance of a large sample cohort for studies on modifier genes influencing disease severity in FAP patients.Hereditary cancer in clinical practice · 2013Article
- Mutational spectrum of the APC and MUTYH genes and genotype-phenotype correlations in Brazilian FAP, AFAP, and MAP patients.Orphanet journal of rare diseases · 2013Article
- A novel pathogenic germline mutation in the adenomatous polyposis coli gene in a Tunisian family with FAP.Familial cancer · 2011Article
- Mutation analysis of the APC gene in Taiwanese FAP families: low incidence of APC germline mutation in a distinct subgroup of FAP families.Familial cancer · 2010Article
- APC and its modifiers in colon cancer.Advances in experimental medicine and biology · 2009Review
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFamilial adenomatous polyposis (FAP) is characterised by variable phenotypic expression. Part of this is attributable to a relationship between APC genotype and phenotype but there remains significant intrafamilial variation. In the Min mouse model of FAP, differences in the severity of gastrointestinal polyposis result from the action of modifier genes.
aimsTo determine whether phenotypic variation in human FAP has an inherited component consistent with the action of modifier genes.
methodWe systematically examined polyp numbers in colectomy specimens from patients with classical FAP. Variation both between and within families was analysed. Formal modelling of the segregation of disease severity in families was performed
resultsThere was strong evidence for a relationship between site of mutation and the number of colorectal polyps, with germline mutations in the "cluster region" causing the most severe disease and those with mutations between codons 1020 and 1169 having the mildest disease. In addition to this genotype-phenotype relationship, we found evidence for non-APC linked genetic modifiers of disease expression. First degree relatives had more similar polyp counts than more distant relatives. Formal modelling of the segregation of disease severity in families revealed further evidence for the action of modifier genes, with a best fit to a mixed model of inheritance.
conclusionOur data provide good evidence to support the hypothesis that modifier genes influence the severity of FAP in humans.
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