INTRODUCTION Familial adenomatous polyposis (FAP) is caused by pathogenic variants in the APC gene. FAP is usually categorized according to phenotype: classical FAP (CFAP) and attenuated FAP (AFAP); the latter is considered to have a milder disease course. We aimed to assess the risk of overall and specific cancers in patients with CFAP and AFAP compared with matched, nonexposed individuals. METHODS All known Danish patients with FAP were classified as either CFAP or AFAP and assigned 4 matched, nonexposed individuals. The risk of overall and specific cancers, and mortality were analyzed. RESULTS The analysis included 311 patients with CFAP, 134 patients with AFAP, and 1,600 nonexposed individuals. The overall cancer risk was significantly higher for both patients with CFAP and AFAP than for nonexposed individuals, with hazard ratios (HRs) of 4.77 (95% confidence interval [CI], 3.61-6.32; P < 0.001) for CFAP and 3.22 (95% CI, 2.16-4.80; P < 0.001) for AFAP. No significant difference was observed when comparing CFAP and AFAP (HR = 1.48; 95% CI, 0.98-2.25; P = 0.0646). The HR of colonic cancer was 2.16 (95% CI, 0.99-7.72; P = 0.0522) and 2.72 (95% CI, 1.19-6.22; P = 0.0177 for CFAP and AFAP), respectively, compared with nonexposed and did not differ between patients with CFAP and AFAP (HR = 0.80; 95% CI, 0.32-2.00; P = 0.6278). Mortality was significantly higher in CFAP (HR = 2.96; 95% CI, 2.04-4.28; P < 0.001), but not in AFAP (HR = 1.40; 95% CI, 0.73-2.69; P = 0.311). DISCUSSION Nationwide data reveal differing risk profiles for specific cancers and mortality in AFAP and CFAP compared with nonexposed individuals. The cancer burden of AFAP necessitates consistent monitoring of these patients.

中文翻译：

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减毒和经典家族性腺瘤性息肉病的癌症风险：具有匹配的、未暴露个体的全国队列。


引言 家族性腺瘤性息肉病 （FAP） 是由 APC 基因的致病性变异引起的。FAP 通常根据表型分类：经典型 FAP （CFAP） 和减毒型 FAP （AFAP）;后者被认为病程较轻。我们旨在评估 CFAP 和 AFAP 患者与匹配的、未暴露的个体相比发生总体和特定癌症的风险。方法 所有已知的丹麦 FAP 患者均被归类为 CFAP 或 AFAP，并分配了 4 个匹配的、未暴露的个体。分析了总体和特定癌症的风险以及死亡率。结果 分析包括 311 例 CFAP 患者、134 例 AFAP 患者和 1,600 例未暴露个体。CFAP 和 AFAP 患者的总体癌症风险均显著高于未暴露个体，风险比 （HR） 为 4.77（95% 置信区间 [CI]，3.61-6.32;P < 0.001） 和 3.22 （95% CI，2.16-4.80;P < 0.001） 对于 AFAP。比较 CFAP 和 AFAP 时未观察到显著差异 （HR = 1.48;95% CI，0.98-2.25;P = 0.0646）。结肠癌的 HR 为 2.16 （95% CI，0.99-7.72;P = 0.0522）和 2.72 （95% CI，1.19-6.22;CFAP 和 AFAP 的 P = 0.0177），与未暴露的患者相比，CFAP 和 AFAP 患者之间没有差异 （HR = 0.80;95% CI，0.32-2.00;P = 0.6278）。CFAP 的死亡率显著更高 （HR = 2.96;95% CI，2.04-4.28;P < 0.001），但在 AFAP 中没有 （HR = 1.40;95% CI，0.73-2.69;P = 0.311）。讨论 全国数据显示，与未暴露的个体相比，AFAP 和 CFAP 的特定癌症和死亡率的风险状况不同。AFAP 的癌症负担需要对这些患者进行持续监测。