+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Multiple approach to the exploration of genotype-phenotype correlations in familial adenomatous polyposis



Multiple approach to the exploration of genotype-phenotype correlations in familial adenomatous polyposis



Journal of Clinical Oncology 21(9): 1698-1707



Familial adenomatous polyposis (FAP), caused by a mutation in the APC gene, is a colorectal cancer predisposition syndrome associated with several other clinical conditions. The severity of the FAP is related to the position of the inherited mutation in the APC gene. We analyzed a large series of FAP patients to identify associations among major clinical manifestations and to correlate the mutation site with specific disease manifestations. APC mutations were identified in 953 FAP patients from 187 families. We used unconditional logistic regression models and a method involving generalized estimating equations to investigate the association between genotype and phenotype. We used multiple correspondence analysis to represent the interrelationships of a multiway contingency table of the considered variables. APC germline mutations were located between codons 156 and 2011 of the APC gene. Mutations spanning the region between codons 543 and 1309 were variable, but strongly associated with congenital hypertrophy of retinal pigment epithelium. Mutations between codons 1310 and 2011 were associated with a six-fold risk of desmoid tumors relative to the low-risk reference region (159 to 495). Mutations at codon 1309 were associated with early development of colorectal cancer. Mutations between codons 976 and 1067 were associated with a three- to four-fold increased risk of duodenal adenomas. The cumulative frequency of extracolonic manifestations was highest for mutations between codons 976 and 1067, followed by mutations between 1310 and 2011. Analysis of the relation between APC mutation site and phenotype identifies subgroups of FAP patients at high risk for major extracolonic disease, which is useful for surveillance and prevention.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 049637243

Download citation: RISBibTeXText

PMID: 12721244

DOI: 10.1200/jco.2003.09.118


Related references

Screening for mutations of the adenomatous polyposis coli gene in 67 Italian familial adenomatous polyposis Further evidence of complex genotype-phenotype correlations. Gastroenterology 114(4 Part 2): A566, 1998

Extended genotype-phenotype correlation in familial adenomatous polyposis A multiple approach to identify a specific APC mutation. Tumori 86(4 Suppl 1): 67, July-August, 2000

Meta-analysis of genotype-phenotype correlations in familial adenomatous polyposis. Gastroenterology 120(5 Suppl. 1): A 739, 2001

Genotype-phenotype correlations as a guide in the management of familial adenomatous polyposis. Clinical Gastroenterology and Hepatology 5(3): 374-378, 2007

Genotype-phenotype correlations in familial adenomatous polyposis and its influence on therapeutic decisions. Gastroenterology 118(4 Suppl 2 Part 1): A43, 2000

Genotype-phenotype correlations of new causative APC gene mutations in patients with familial adenomatous polyposis. Journal of Medical Genetics 32(9): 728-731, 1995

Dominant negative effect of the APC1309 mutation: a possible explanation for genotype-phenotype correlations in familial adenomatous polyposis. Cancer Research 59(8): 1857-1860, 1999

APC germ-line mutations in southern Spanish patients with familial adenomatous polyposis: genotype-phenotype correlations and identification of eight novel mutations. Genetic Testing 9(1): 37-40, 2005

Prospective evaluation of duodenal polyposis progression in familial adenomatous polyposis patients, and genotype-phenotype correlation. Gastroenterology 118(4 Suppl 2 Part 1): AGA A656, 2000

Genotype-phenotype correlation in familial adenomatous polyposis. Gastroenterology 108(4 Suppl. ): A459, 1995

Genotype-phenotype correlations in attenuated adenomatous polyposis coli. American Journal of Human Genetics 62(6): 1290-1301, 1998

Genotype-phenotype correlations at the adenomatous polyposis coli (APC) gene. Critical Reviews in Oncogenesis 6(3-6): 291-303, 1995

The complex genotype-phenotype relationship in familial adenomatous polyposis. European Journal of Gastroenterology and Hepatology 16(1): 5-8, 2004

Genotype-phenotype correlations in patients with attenuated adenomatous polyposis coli. Gastroenterology 114(4 Part 2): A682, 1998

Genotype and phenotype of patients with both familial adenomatous polyposis and thyroid carcinoma. Familial Cancer 2(2): 95-99, 2003