Cancer Risks in Attenuated and Classical Familial Adenomatous Polyposis: A Nationwide Cohort With Matched, Nonexposed Individuals

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.