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COLON CANCER |
1 Polyposis Registry, Cancer Research UK Colorectal Cancer Unit, St Mark’s Hospital, Harrow, Middlesex, UK
2 Statistics Consultancy, 13 Allonby Drive, Ruislip, Middlesex, UK
3 Colorectal Cancer Genetics and Polyposis Registry, Cancer Research UK Colorectal Cancer Unit, St Mark’s Hospital, Harrow, Middlesex, UK, and Molecular and Population Genetics, Cancer Research UK, 44 Lincoln’s Inn Fields, London, UK
4 Colorectal Cancer Genetics and Polyposis Registry, Cancer Research UK Colorectal Cancer Unit, St Mark’s Hospital, Harrow, Middlesex, UK
Correspondence to:
Correspondence to:
Professor R K S Phillips
Polyposis Registry, St Mark’s Hospital, Harrow, Middlesex HA1 3UJ, UK; marie.gun{at}cancer.org.uk
ABSTRACT
Background: Many patients with familial adenomatous polyposis (FAP) die from desmoid tumours which can arise spontaneously but often appear to be surgically induced by prophylactic colectomy. FAP results from germline adenomatous polyposis coli (APC) gene mutations and desmoids arise following biallelic APC mutation, with one change usually occurring distal to the second ß-catenin binding/degradation repeat of the gene (3' to codon 1399). We have suggested that because families with germline mutations in this region already have the requisite change, they are more likely to develop desmoids. However, there are families with 5' germline mutations where desmoids are common.
Patients and methods: We examined desmoid risk dependent on germline APC mutation, sex, history of abdominal surgery, and family history in FAP patients from the St Mark’s Hospital Polyposis Registry.
Results: Overall desmoid prevalence was 15%. Desmoids tended to cluster in susceptible individuals, irrespective of the germline APC mutation. Independent predictors of increased desmoid risk were: germline mutation distal to codon 1399; any family history of disease; and a strong family history of desmoids. A family history of multiple desmoids (>1) increased an individual’s own risk of multiplicity. Females had twice the odds of developing desmoids compared with males. There was no significant interaction between any of the three explanatory variables.
Conclusions: Our results indicate the influence of unknown genetic factors independent of APC in susceptibility to desmoid tumours in FAP. The data have implications in terms of clinical management of FAP patients and assessing the balance between chemoprevention and prophylactic colectomy.
Abbreviations: FAP, familial adenomatous polyposis; APC, adenomatous polyposis coli gene; LOH, loss of heterozygosity
Keywords: familial adenomatous polyposis; desmoid tumours; adenomatous polyposis coli gene; family history
This article has been cited by other articles:
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  H F A Vasen, G Moslein, A Alonso, S Aretz, I Bernstein, L Bertario, I Blanco, S Bulow, J Burn, G Capella, et al. Guidelines for the clinical management of familial adenomatous polyposis (FAP) Gut, May 1, 2008; 57(5): 704 - 713. [Abstract] [Full Text] [PDF]
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 A. Latchford, E. Volikos, V. Johnson, P. Rogers, N. Suraweera, I. Tomlinson, R. Phillips, and A. Silver APC mutations in FAP-associated desmoid tumours are non-random but not 'just right' Hum. Mol. Genet., January 1, 2007; 16(1): 78 - 82. [Abstract] [Full Text] [PDF]
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 M. Gega, H. Yanagi, R. Yoshikawa, M. Noda, H. Ikeuchi, K. Tsukamoto, T. Oshima, Y. Fujiwara, N. Gondo, K. Tamura, et al. Successful Chemotherapeutic Modality of Doxorubicin Plus Dacarbazine for the Treatment of Desmoid Tumors in Association With Familial Adenomatous Polyposis J. Clin. Oncol., January 1, 2006; 24(1): 102 - 105. [Abstract] [Full Text] [PDF]
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