Bertario L, Russo A, Sala P, Eboli M, Giarola M, D'amico F, Gismondi V, Varesco L, Pierotti M A, Radice P
Department of Surgery, National Cancer Institute, Milan, Italy.
Int J Cancer. 2001 Mar 20;95(2):102-7. doi: 10.1002/1097-0215(20010320)95:2<102::aid-ijc1018>3.0.co;2-8.
Desmoids represent the most important cause of death, after colorectal cancer, in patients affected with familial adenomatous polyposis (FAP), an inherited 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 occurrence of desmoids, colorectal cancer and other extra-colonic manifestations were 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. Desmoids 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 (OR = 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 with patients with mutations located upstream. Mutations beyond codon 1309 conferred a 17-fold higher risk, compared with mutations upstream codon 452. Multivariate analysis identified as independent predictors mutation beyond codon 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 integrating genetic and clinical data is helpful in defining subgroups of patients at higher risk for desmoids, who may benefit from specific prevention programs.
硬纤维瘤是家族性腺瘤性息肉病（FAP）患者继结直肠癌之后的最重要死因，FAP是一种由于APC基因突变导致的遗传性疾病。我们研究的目的是评估FAP患者发生硬纤维瘤的风险，并评估硬纤维瘤与不同风险因素之间的关联。我们对897例FAP患者的硬纤维瘤、结直肠癌及其他结肠外表现的发生情况进行了评估，其中653例患者还进行了APC基因突变检测。使用无条件多因素logistic回归模型计算比值比（OR）及相应的95%置信区间（CI）。107例患者（11.9%）发生了硬纤维瘤，累积风险为20.6%。女性的风险显著高于男性（OR = 2.1；95% CI 1.4 - 3.1）。硬纤维瘤家族史（OR = 8.75；95% CI 5.66 - 13.51）、骨瘤（OR = 2.9；95% CI 1.8 - 4.8）和表皮样囊肿（OR = 1.8；95% CI 1.1 - 3.2）也与疾病的发生显著相关。与位于密码子1444上游发生突变的患者相比，密码子1444以外发生APC基因突变的患者风险增加了12倍。与密码子452上游发生突变相比，密码子1309以外的突变使风险增加了17倍。多因素分析确定密码子1444以外的突变（OR = 6.2；95% CI 2.5 - 15.8）、硬纤维瘤家族史（OR = 5.8；95% CI 3.1 - 10.6）、女性性别（OR = 2.1；95% CI 1.1 - 3.8）和骨瘤的存在（OR = 1.9；95% CI 1.1 - 3.4）为独立预测因素。我们的结果表明，整合遗传和临床数据有助于确定硬纤维瘤高风险患者亚组，这些患者可能从特定的预防方案中获益。
