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 CFAP and AFAP patients compared to matched, non-exposed individuals. METHODS All known Danish FAP patients were classified as either CFAP or AFAP and assigned four matched, non-exposed individuals. The risk of overall and specific cancers, and mortality were analyzed. RESULTS The analysis included 311 CFAP patients, 134 AFAP patients, and 1,600 non-exposed individuals. The overall cancer risk was significantly higher for both CFAP and AFAP patients than for non-exposed individuals, with hazard ratios (HR) 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 to non-exposed and did not differ between CFAP and AFAP patients (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). CONCLUSION Nationwide data reveal differing risk profiles for specific cancers and mortality in AFAP and CFAP compared to non-exposed individuals. The cancer burden of AFAP necessitates consistent monitoring of these patients.

中文翻译：

---

减毒和经典家族性腺瘤性息肉病的癌症风险：匹配的、未暴露个体的全国队列：AFAP 和 FAP 患者的癌症和手术。


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 患者与匹配的非暴露个体相比患总体和特定癌症的风险。方法 所有已知的丹麦 FAP 患者被归类为 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） 的 AS 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），分别与未暴露患者相比，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）。结论 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。