Risk of desmoid tumor based on APC pathogenic variant location and surgical history in familial adenomatous polyposis: a U.S. community cohort study.

APC

Germline pathogenic APC variants, with desmoid tumour risk modulated by variant location (codons 600 to 1600) and by prior colorectal surgery

Desmoid tumours are a leading cause of morbidity and mortality in familial adenomatous polyposis, yet available risk data come mostly from registries and tertiary referral centres. This retrospective cohort included 328 patients carrying a pathogenic or likely pathogenic APC variant identified through the Kaiser Permanente Northern California community-based system, which serves 4.6 million members; 36 of them (11.0%) developed a desmoid tumour. Risk was highest for centrally located variants (codons 600 to 1600), and family history was independently associated with it (adjusted odds ratio 4.34; 95% CI 1.12-16.86). All colorectal surgeries were associated with significantly elevated risk: ileostomy (adjusted OR 12.07; 2.10-69.47), subtotal colectomy with ileorectal anastomosis (9.03; 1.63-49.96) and total proctocolectomy with ileal pouch-anal anastomosis (10.98; 2.12-56.81), whereas non-colorectal surgery was not (adjusted OR 0.73).

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The value lies in recruitment: a community population of 4.6 million members corrects the bias of tertiary-centre series, where complicated cases are over-represented, so an 11.0% desmoid tumour rate is a more reliable benchmark for presurgical counselling. The practical finding is however a negative one: all three surgical constructions carry the same order of risk, so the choice between ileorectal and ileal pouch-anal anastomosis cannot be decided on desmoid risk. The confidence intervals, very wide for only 36 events (up to 2.10-69.47), mean these odds ratios should be presented as orders of magnitude rather than as figures usable at face value.

Analysis by Dr Thibaut Benquey