Risk factors predicting intra-abdominal desmoids in familial adenomatous polyposis: a single centre experience.
BACKGROUND
Desmoids are myofibroblastic proliferations occurring in 15% of patients with familial adenomatous polyposis (FAP), 70% being intra-abdominal desmoids (IAD). Since the morbidity and mortality due to desmoids is almost entirely attributable to IAD, we aimed to identify specifically risk factors predicting IAD development in FAP.


METHODS
We undertook a retrospective review of our institutional database. Multivariate analysis was performed, and hazard ratios (HR) calculated for variables including female gender, 3' APC mutation, surgical intervention for FAP (colectomy with ileo-rectal anastomosis or restorative proctocolectomy), age at surgery and family history (FH) of desmoids.


RESULTS
Of the 558 patients analysed, 49 (9%) developed IAD; 22 (4%) diagnosed intra-operatively and 27 (5%) developing over a median post-operative period of 34 (7-120) months. 75% of IAD had developed before age 40. A 3' APC mutation (HR 5.2, 95% CI 2.1-13.3, P = 0.001), positive FH (HR 2.5, 95% CI 1.4-4.6, P = 0.003) and female gender (HR 1.9, 95% CI 1.0-3.5, P = 0.04) were found to be predictive of IAD development. No significant difference in IAD risk was detected between the type of surgical intervention (P = 0.37) or age at surgery (P = 0.29).


CONCLUSIONS
Our analysis confirms 3' APC mutation to be the most significant risk factor for IAD development. The independent association between positive FH and IAD risk suggests the existence of modifier genes, independent of the APC genotype-phenotype correlation. Few of these risk factors can be meaningfully modified. Delaying prophylactic surgery may be appropriate in female patients with a 3' APC mutation and attenuated polyposis.
Sinha
A
A
St. Mark's Hospital and Imperial College, London, HA1 3UJ, UK.
Tekkis
P P
PP
Neale
K F
KF
Phillips
R K S
RK
Clark
S K
SK
D011125:Adenomatous Polyposis Coli / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D015331:Cohort Studies; D003082:Colectomy; D005260:Female; D018221:Fibromatosis, Abdominal / Q000453:epidemiology* / Q000473:pathology / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult