Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA.
Harvard Medical School, Boston, MA.
JAMA. 2012 Aug 1;308(5):485-492. doi: 10.1001/jama.2012.8780.
CONTEXT: Patients with multiple colorectal adenomas may carry germline mutations in the APC or MUTYH genes. OBJECTIVES: To determine the prevalence of pathogenic APC and MUTYH mutations in patients with multiple colorectal adenomas who had undergone genetic testing and to compare the prevalence and clinical characteristics of APC and MUTYH mutation carriers. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study conducted among 8676 individuals who had undergone full gene sequencing and large rearrangement analysis of the APC gene and targeted sequence analysis for the 2 most common MUTYH mutations (Y179C and G396D) between 2004 and 2011. Individuals with either mutation underwent full MUTYH gene sequencing. APC and MUTYH mutation prevalence was evaluated by polyp burden; the clinical characteristics associated with a pathogenic mutation were evaluated using logistic regression analyses. MAIN OUTCOME MEASURE: Prevalence of pathogenic mutations in APC and MUTYH genes. RESULTS: Colorectal adenomas were reported in 7225 individuals; 1457 with classic polyposis (≥100 adenomas) and 3253 with attenuated polyposis (20-99 adenomas). The prevalence of pathogenic APC and biallelic MUTYH mutations was 95 of 119 (80% [95% CI, 71%-87%]) and 2 of 119 (2% [95% CI, 0.2%-6%]), respectively, among individuals with 1000 or more adenomas, 756 of 1338 (56% [95% CI, 54%-59%]) and 94 of 1338 (7% [95% CI, 6%-8%]) among those with 100 to 999 adenomas, 326 of 3253 (10% [95% CI, 9%-11%]) and 233 of 3253 (7% [95% CI, 6%-8%]) among those with 20 to 99 adenomas, and 50 of 970 (5% [95% CI, 4%-7%]) and 37 of 970 (4% [95% CI, 3%-5%]) among those with 10 to 19 adenomas. Adenoma count was strongly associated with a pathogenic mutation in multivariable analyses. CONCLUSIONS: Among patients with multiple colorectal adenomas, pathogenic APC and MUTYH mutation prevalence varied considerably by adenoma count, including within those with a classic polyposis phenotype. APC mutations predominated in patients with classic polyposis, whereas prevalence of APC and MUTYH mutations was similar in attenuated polyposis. These findings require external validation.
背景：有多发性结直肠腺瘤的患者可能携带 APC 或 MUTYH 基因的种系突变。
目的：确定接受基因检测的多发性结直肠腺瘤患者中致病性 APC 和 MUTYH 突变的流行率，并比较 APC 和 MUTYH 突变携带者的流行率和临床特征。
设计、地点和参与者：这是一项在 2004 年至 2011 年间进行的横断面研究，共纳入了 8676 名个体，这些个体接受了 APC 基因的全基因测序和大片段重排分析，以及最常见的 2 种 MUTYH 突变（Y179C 和 G396D）的靶向序列分析。有任一种突变的个体均接受了全 MUTYH 基因突变测序。通过腺瘤负担评估 APC 和 MUTYH 基因突变的流行率；使用逻辑回归分析评估与致病性突变相关的临床特征。
主要结局测量：APC 和 MUTYH 基因中致病性突变的流行率。
结果：7225 名个体报告了结直肠腺瘤；1457 名具有经典息肉病（≥100 个腺瘤），3253 名具有轻度息肉病（20-99 个腺瘤）。在有 1000 个或更多腺瘤的个体中，致病性 APC 和双等位基因 MUTYH 突变的流行率分别为 95/119（80%[95%CI，71%-87%]）和 2/119（2%[95%CI，0.2%-6%]）；在有 100-999 个腺瘤的个体中，分别为 756/1338（56%[95%CI，54%-59%]）和 94/1338（7%[95%CI，6%-8%]）；在有 20-99 个腺瘤的个体中，分别为 326/3253（10%[95%CI，9%-11%]）和 233/3253（7%[95%CI，6%-8%]）；在有 10-19 个腺瘤的个体中，分别为 50/970（5%[95%CI，4%-7%]）和 37/970（4%[95%CI，3%-5%]）。多变量分析显示，腺瘤计数与致病性突变密切相关。
结论：在有多发性结直肠腺瘤的患者中，致病性 APC 和 MUTYH 突变的流行率因腺瘤计数而异，包括具有经典息肉病表型的患者。APC 突变在经典息肉病患者中占主导地位，而在轻度息肉病中 APC 和 MUTYH 突变的流行率相似。这些发现需要外部验证。
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