Genotype and phenotype factors as determinants of desmoid tumors in patients with familial adenomatous polyposis

Desmoids represent the most important cause of death, after colorectal canc er, in patients affected with familial adenomatous polyposis (FAP), an inhe rited disease due to mutations in the APC gene. The aims of our study were to estimate the risk of developing desmoids in FAP patients and to evaluate the association between desmoids and different risk factors. The occurrenc e of desmoids, colorectal cancer and other extra-colonic manifestations wer e assessed in 897 FAP patients, 653 of whom were also investigated for APC mutations. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were computed using an unconditional multiple logistic regression model. D esmoids developed in 107 patients (11.9%), with a cumulative risk of 20.6%, Females had a significantly higher risk than males (OR = 2.1; 95% CI 1.4-3 .1). Family history of desmoids (OR = 8.75; 95% CI 5.66-13.51), osteomas (O R = 2.9; 95% CI 1.8-4.8) and epidermoid cysts (OR 1.8; 95% CI 1.1-3.2) was also significantly associated with the occurrence of disease. Subjects with APC mutations beyond codon 1444 had a 12-fold increased risk, compared wit h patients with mutations located upstream. Mutations beyond codon 1309 con ferred a 17-fold higher risk, compared with mutations upstream codon 452. M ultivariate analysis identified as independent predictors mutation beyond c odon 1444 (OR = 6.2; 95% CI 2.5-15.8), family history of desmoids (OR 5.8; 95% CI 3.1-10.6), female gender (OR = 2.1;95% CI 1.1-3.8) and the presence of osteomas (OR = 1.9; 95% CI 1.1-3.4). Our results indicate that integrati ng genetic and clinical data is helpful in defining subgroups of patients a t higher risk for desmoids, who may benefit from specific prevention progra ms. (C) 2001 Wiley-Liss, Inc.