Genetic testing and phenotype in a large kindred with attenuated familial adenomatous polyposis
Genetic testing and phenotype in a large kindred with attenuated familial adenomatous polyposis
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DOI：
10.1053/j.gastro.2004.05.003
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发表时间：
2004-08-01
期刊：
影响因子：
29.4
通讯作者：
White, RL
中科院分区：
文献类型：
--
作者：
Burt, RW;Leppert, MF;White, RL
背景与目的：家族性腺瘤性息肉病的一种减毒形式已被描述，但其表型仍知之甚少。研究方法：我们对810名来自2个减毒家族性腺瘤性息肉病家族的个体进行了基因检测，这些个体具有相同的生殖系腺瘤性息肉病结肠基因突变。对突变阳性者进行结肠镜检查。结果：184例患者存在致病突变。在120名平均年龄为41岁的基因携带者中，有111人存在腺瘤性息肉。腺瘤的中位数为25（范围0 - 470），息肉的数量变化显著，近端结肠息肉占优势。27例突变携带者（平均年龄58岁，范围29 - 81岁）发生结直肠癌，其中75%发生在近端结肠。到80岁时患结直肠癌的累积风险估计为69%。在平均7.8年（范围，1 - 34年）的结肠切除术后直肠残留物中平均发现3.4个复发性息肉（范围，0 - 29个），其中1个直肠癌。结论：这项研究表明，在所检查的运动中，减弱的家族性腺瘤性息肉病显示出比典型的家族性腺瘤性息肉病小得多的息肉中位数，即使在老年，息肉数量也有很大的变化，息肉和癌症的位置更接近结肠，但它与极高的结肠癌风险相关。减毒家族性腺瘤性息肉病的表型在某些情况下模仿典型的家族性腺瘤性息肉病，但在其他情况下难以与散发性腺瘤和结直肠癌区分，因此使基因检测特别重要。
Background & Aims: An attenuated form of familial adenomatous polyposis has been described, but the phenotype remains poorly understood. Methods: We performed genetic testing on 810 individuals from 2 attenuated familial adenomatous polyposis kindreds harboring an identical germline adenomatous polyposis coli gene mutation. Colonoscopy was performed on mutation-positive persons. Results: The disease-causing mutation was present in 184 individuals. Adenomatous polyps were present in 111 of 120 gene carriers who had colonoscopy at an average age of 41 years. The median number of adenomas was 25 (range, 0-470), with striking variability of polyp numbers and a proximal colonic predominance of polyps. Colorectal cancer occurred in 27 mutation carriers (average age, 58 years; range, 29-81 years), with 75% in the proximal colon. The cumulative risk of colorectal cancer by age 80 was estimated to be 69%. An average of 3.4 recurrent polyps (range, 0-29) were found in the postcolectomy rectal remnant over a mean of 7.8 years (range, 1-34 years), with 1 rectal cancer. Conclusions: This investigation shows that attenuated familial adenomatous polyposis in the kindreds examined shows a much smaller median number of polyps than typical familial adenomatous polyposis, a wide variability in polyp number even at older ages, and a more proximal colonic location of polyps and cancer, yet it is associated with an extremely high risk of colon cancer. The phenotype of attenuated familial adenomatous polyposis mimics typical familial adenomatous polyposis in some cases but in others is difficult to distinguish from sporadic adenomas and colorectal cancer, thus making genetic testing particularly important.