Introduction
Familial adenomatous polyposis (FAP) is a dominantly inherited disorder that predisposes to colorectal cancer. However, after the introduction of prophylactic colectomy and endoscopic surveillance, as well as genetic screening of first-degree family members, the risk of CRC has decreased dramatically with subsequent prolonged expected life expectancy.1 Current guidelines solely aim at preventing cancer, which has been the focus for decades.2-3 From a patient perspective, mental aspects of the disease, which might decrease quality of life may be equally important. However, knowledge and focus on mental well-being in FAP patients is limited. If FAP patients are at increased risk of mental stress and ultimately of developing psychiatric disorders, a potential possibility of early intervention is missed. The Danish Polyposis Register has for over 40 years included data from all Danish FAP patients. Consequently, the register is free of referral and selection bias. We aimed this study at estimating the impact on educational level and risk of psychiatric disorders in a nationwide cohort of patients with FAP compared to a matched background population.
Aims & Methods
Known Danish FAP patients by April 2021 were identified from the Danish Polyposis Register and paired with four matched controls based on matched on sex, birth year, and zip code at birth. Using national registries, educational status, psychiatric contacts or diagnoses, and need for antidepressants, anxiolytics, or antipsychotics were compared between FAP patients and controls. Follow-up of patients started on the date of their first being identified as having FAP or on 1st January 1996, whichever came last. Follow-up ended on the date of any of the listed outcomes, emigration, death, loss to follow-up or the end of the study on 1st January 2020, whichever came first. Relative risk for any of the listed outcomes was quantified by hazard ratios (HR); these were estimated using Cox proportional hazards regression, with age as the underlying timescale, and used the variables of exposure status, year of outcome, sex, cancer, and education for the multiple regression model. Cancer was included as a time-varying covariate in the Cox proportional hazards regressions.
Results
The analysis included 445 FAP patients and 1,538 controls. The highest attained education was significantly lower for FAP patients (p<0.001). When comparing FAP patients and controls and adjusting for cancer diagnosis, an increased risk was observed for a psychiatric contact (1.69, CI 95%, 1.25–2.29, p<0.001), any psychiatric prescription (1.39, CI 95%, 1.17–1.66, p<0.001), receiving a psychiatric diagnosis (1.64, CI 95%, 1.19–2.26, p=0.002), as well as facing any psychiatric event (HR 1.55, CI 95%, 1.32–1.83, p<0.001). An increased risk was specifically seen for affective (1.76, CI 95%, 1.09–2.83, p=002) and behavioral disorders (2.01, CI 95%, 1.10–3.69, p=0.02) as well as prescription of antidepressants (1.59, CI 95%, 1.24–2.03, p<0.001) and antipsychotics (1.85, CI 95%, 1.26–2.70, p=0.002). For FAP patients, the median age for affective and behavioral disorders was 32.7 years (range 15.0–73.6 years) and 14.7 years (range 5.5–47.7 years), respectively, which did not differ from controls.
Conclusion
Compared to controls, FAP patients have a significantly reduced educational level and an increased risk of developing affective and behavioural disorders with increased needs for antidepressants and antipsychotics. This calls for further exploratory and interventional trials.
References
1 Karstensen JG, Burisch J, Pommergaard HC, et al. Colorectal Cancer in Individuals With Familial Adenomatous Polyposis, Based on Analysis of the Danish Polyposis Registry. Clin Gastroenterol Hepatol 2019; 17(11): 2294-300 e1.
2 Monahan KJ, Bradshaw N, Dolwani S, et al. Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG). Gut 2020;69(3):411-44.
3 van Leerdam ME, Roos VH, van Hooft JE, et al. Endoscopic management of polyposis syndromes: European society of gastrointestinal endoscopy
(ESGE) guideline. Endoscopy 2019;51:877–95.
Disclosure
JGK is consultant for SNIPR BIOME
