Church James, Xhaja Xhileta, LaGuardia Lisa, O'Malley Margaret, Burke Carol, Kalady Matthew
Sanford R. Weiss Center, M.D., for Hereditary Colorectal Cancer, Department of Colorectal Surgery, Digestive Diseases Institute, Cleveland Clinic Foundation, Cleveland, Ohio.
Dis Colon Rectum. 2015 Apr;58(4):444-8. doi: 10.1097/DCR.0000000000000316.
Desmoid disease can be a serious, life-threatening complication of familial adenomatous polyposis. The ability to predict patients at increased desmoid risk is important, but a convincing genotype-phenotype correlation for desmoid formation has not yet been described.
The aim of this study is to assess the relationship between desmoid disease and genotype in patients with familial adenomatous polyposis.
This is a cohort study.
All patients with familial adenomatous polyposis and a documented pathogenic APC mutation in themselves or a first-degree relative were selected.
The comparison of genotype and the presence, stage, and site of desmoid disease are the primary end points of this study.
Three hundred twenty-three patients from 219 families were identified. Mutations spanned the length of the gene, from codon 213 to codon 2051. Desmoid disease was diagnosed in 77 patients from 68 families. Desmoid disease was found in 14.9% of patients with a mutation 5' of codon 400, 23.2% of patients with a mutation from codon 401 to 1400, and in 37.1% of those with a mutation 3' of 1400. All patients with 5' mutations had stage I or II abdominal desmoid disease, and all tumors were stable or shrinking. Twelve percent of patients who had desmoid disease with mutations between codons 400 and 1400 had stage III or IV desmoid disease, and 5 of 42 (12%) tumors were growing at the time of the study. There had been 2 desmoid-related deaths. Almost half (44%) of patients who had desmoid disease with mutations 3' of codon 1400 had stage III or IV disease. Three of 14 tumors were growing (21%), and there were 4 desmoid-related deaths.
This study was conducted at a tertiary referral center, and there was no systematic surveillance for desmoids.
Desmoid disease occurs in patients who have familial adenomatous polyposis with almost any APC mutation, although there is an increased propensity in those with a 3' mutation. The incidence and severity of the desmoid disease are related to the site of the mutation.
硬纤维瘤病可能是家族性腺瘤性息肉病的一种严重的、危及生命的并发症。预测硬纤维瘤风险增加的患者的能力很重要，但尚未描述令人信服的硬纤维瘤形成的基因型-表型相关性。
本研究的目的是评估家族性腺瘤性息肉病患者中硬纤维瘤病与基因型之间的关系。
这是一项队列研究。
选择所有自身或一级亲属有记录的致病性APC突变的家族性腺瘤性息肉病患者。
基因型与硬纤维瘤病的存在、分期和部位的比较是本研究的主要终点。
确定了来自219个家庭的233名患者。突变跨越基因全长，从第213密码子到第2051密码子。68个家庭的77名患者被诊断为硬纤维瘤病。在密码子400上游有突变的患者中，14.9%发生了硬纤维瘤病；在密码子401至1400之间有突变的患者中，23.2%发生了硬纤维瘤病；在密码子1,400下游有突变的患者中，37.1%发生了硬纤维瘤病。所有密码子上游有突变的患者均患有I期或II期腹部硬纤维瘤病，所有肿瘤均稳定或缩小。密码子400和1400之间有突变且患有硬纤维瘤病的患者中，12%患有III期或IV期硬纤维瘤病，在研究时42个肿瘤中有5个（12%）正在生长。有2例与硬纤维瘤相关的死亡。密码子1400下游有突变且患有硬纤维瘤病的患者中，近一半（44%）患有III期或IV期疾病。14个肿瘤中有3个（21%）正在生长，有4例与硬纤维瘤相关的死亡。
本研究在一家三级转诊中心进行，没有对硬纤维瘤进行系统监测。
几乎任何APC突变的家族性腺瘤性息肉病患者都会发生硬纤维瘤病，尽管密码子下游有突变的患者发病倾向增加。硬纤维瘤病的发病率和严重程度与突变位点有关。
