Guidelines for the clinical management of familial adenomatous polyposis (FAP)

Vasen, Hans F. A.; Möslein, Gabriela; Alonso, Ángel; Aretz, Stefan; Bernstein, Inge; Bertario, Lucio; Blanco, Ignacio; Bülow, Steffen; Burn, John; Capellà, Gabriel; Colas, Chrystelle; Engel, Christoph; Frayling, Ian Martin; Friedl, Waltraut; Hes, Frederik J.; Hodgson, Shirley; Järvinen, Heikki; Mecklin∥, Jukka–Pekka; Møller, Pål; Myrhoi, T.; Nagengast, Fokko M.; Parc, Yann; Phillips, R. K. S.; Clark, Susan; Leòn, Maurizio Ponz de; Renkonen–Sinisalo, Laura; Sampson, Julian R.; Stormorken, Astrid; Tejpar, Sabine; Thomas, Huw; Wijnen, Juul T.

doi:10.1136/gut.2007.136127

Cited by 619 publications

(592 citation statements)

References 93 publications

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“…Although heterogeneous, our study population was representative of FAP patients because all clinical findings (colonic and extracolonic manifestations) were present in proportions previously reported in other FAP cohorts. (1,28) In our study population, mean P1NP and b-CTX concentrations were within the normal ranges and were significantly positively correlated. Both these markers also were positively correlated with BMD.…”

Section: Discussionsupporting

confidence: 48%

“…This observation is in keeping with previous reports indicating that osteomas are more prevalent in young FAP patients. (1) However, it is well documented that osteomas may resolve spontaneously, (43,44) so we cannot exclude the possibility, owing to the cross-sectional design of our study, that some of the patients without any present sign of osteoma(s) may have had this pathology in the past.…”

Section: Discussionmentioning

confidence: 86%

“…Occurring in approximately 1:10,000 live births, FAP is characterized by the development of hundreds to thousands of colorectal adenomatous polyps during childhood and adolescence. (1) The adenomas inevitably progress to colorectal carcinoma (CRC) at a mean age of 40 to 50 years if colectomy is not performed. (2) FAP is also associated with an increased risk of extracolonic malignancies (eg, duodenal, pancreatic, and thyroid cancer) and other pathologic conditions, such as osteomas, dental anomalies, epidermoid cysts, lipomas, desmoid tumors, and congenital hypertrophy of the retinal pigment epithelium (CHRPE).…”

Section: Introductionmentioning

confidence: 99%

“…(4) Genetic analysis identifies gene-inactivating mutations within the APC gene in more than 70% of patients. (1) The APC tumor-suppressor gene is located on chromosome 5q21-q22 and consists of 15 exons that encode a large multifunctional protein product (312 kDa, 2843 codons) known ORIGINAL ARTICLE J JBMR to be involved in a broad spectrum of cellular processes such as cell cycle regulation, apoptosis, cell adhesion and migration, microtubule assembly, cell fate determination, and chromosomal stability. (5) However, APC's main tumor-suppressor function is to bind to and to downregulate the key transducer of the canonical Wnt signaling pathway, b-catenin, thereby acting as a strong negative regulator of the Wnt signaling cascade.…”

Section: Introductionmentioning

confidence: 99%

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APC mutations are associated with increased bone mineral density in patients with familial adenomatous polyposis

Miclea

Karperien

Langers

et al. 2010

Journal of Bone and Mineral Research

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The canonical Wnt pathway plays a key regulatory role in osteoblastogenesis and bone mass acquisition through its main effector, bcatenin. Adenomatous polyposis coli (APC) represents the key intracellular gatekeeper of b-catenin turnover, and heterozygous germline mutations in the APC gene cause familial adenomatous polyposis (FAP). Whether APC mutations affect bone mass has not been previously investigated. We conducted a cross-sectional study evaluating skeletal status in FAP patients with a documented APC mutation. Twenty-two FAP patients with a mean age of 42 years (54.5% women) were included in this study. Mean bone mineral density (BMD) Z-scores were significantly increased above normal at all measured sites: lumbar spine (p < .01), total hip (p < .01), femoral neck (p < .05), and trochanter (p < .01). Z-scores were þ1 or greater in 14 patients (63.6%) and þ2 or greater in 5 (22.7%). Mean values of bone turnover markers were within normal ranges. There was a significant positive correlation between procollagen type I N-terminal propeptide (P1NP) and b-crosslaps (b-CTX) (r ¼ 0.70, p < .001) and between these markers and sclerostin and BMD measurements. We demonstrate that FAP patients display a significantly higher than normal mean BMD compared with age-and sex-matched healthy controls in the presence of a balanced bone turnover. Our data suggest a state of ''controlled'' activation of the Wnt signaling pathway in heterozygous carriers of APC mutations, most likely owing to upregulation of cytoplasmic b-catenin levels. ß

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Section: Discussionsupporting

confidence: 48%

Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

APC mutations are associated with increased bone mineral density in patients with familial adenomatous polyposis

Miclea

Karperien

Langers

et al. 2010

Journal of Bone and Mineral Research

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“…The pathogenetic mechanisms of the rarer Gardner fibromas are still unknown. As 15-20% of constitutional APC variants occur de novo 8 and fibromatous soft tissue lesions may be the first manifestation in FAP patients, genetic characterization of these tumors, especially in children, may help to identify FAP patients. We report the cytogenetic, molecular genetic, and immunohistochemical characterization of two Gardner fibromas, which allowed the identification of two previously unrecognized FAP families with constitutional APC variants.…”

Section: Introductionmentioning

confidence: 99%

Identification of previously unrecognized FAP in children with Gardner fibroma

et al. 2014

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Fibromatous soft tissue lesions, namely desmoid-type fibromatosis and Gardner fibroma, may occur sporadically or as a result of inherited predisposition (as part of familial adenomatous polyposis, FAP). Whereas desmoid-type fibromatosis often present b-catenin overexpression (by activating CTNNB1 somatic variants or APC biallelic inactivation), the pathogenetic mechanisms in Gardner fibroma are unknown. We characterized in detail Gardner fibromas diagnosed in two infants to evaluate their role as sentinel lesions of previously unrecognized FAP. In the first infant we found a 5q deletion including APC in the tumor and the novel APC variant c.4687dup in constitutional DNA. In the second infant we found the c.5826_5829del and c.1678A4T APC variants in constitutional and tumor DNA, respectively. None of the constitutional APC variants occurred de novo and both tumors showed nuclear staining for b-catenin and no CTNNB1 variants. We present the first comprehensive characterization of the pathogenetic mechanisms of Gardner fibroma, which may be a sentinel lesion of previously unrecognized FAP families.

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