Introduction

Familial adenomatous polyposis (FAP) is a hereditary disorder that predisposes patients to colorectal cancer (CRC). Prophylactic colectomy has greatly reduced the risk of CRC. However, new associations between FAP and the risk of other cancers have subsequently emerged. In this study, we aimed to assess the risk of specific primary and secondary cancers among FAP patients in comparison with matched controls.

Aims & Methods

All known FAP patients up until April 2021 were identified in the nationwide Danish Polyposis Register and paired with four unique controls matched by birth year, sex, and zip code. Risk of overall cancers, specific cancer types, and risk of a second primary cancer were assessed and compared with controls.

Results

The analysis included 565 FAP patients and 1,890 controls. The overall risk of cancer was significantly higher for FAP patients than controls (hazard ratio (HR): 4.12, CI 95%, 3.28-5.17, p<0.001). The increased risk was mainly due to CRC (HR: 4.61, CI 95% 2.58-8.22, p<0.001), pancreatic cancer (HR: 6.45, CI 95% 2.02-20.64, p=0.002), and duodenal/small bowel cancer (HR: 14.49, CI 95% 1.76-119.47, p=0.013), while no significant difference was observed for gastric cancer (HR: 3.29, CI 95% 0.53-20.23, p=0.20). Furthermore, the risk of a second primary cancer was significantly higher for FAP patients (HR: 1.89, CI 95% 1.02-3.50, p=0.042). After 15 years, the point estimates for FAP patients and controls were 83.6 % vs. 94.8% being alive without cancer, 7.2% vs. 1.9% developing cancer, and 15.1% vs. 3.4% were deceased, respectively. When extending the period to 30 years, 60.7% vs. 81.1% were alive without cancer, 11.4% vs. 5.6% developed cancer, and 27.9% vs. 13.4% were deceased for FAP patients and controls, respectively. Between 1980 and 2020, the risk of cancer among FAP patients decreased by approximately 50%.

Conclusion

Analyzing national data for Danish polyposis patients and matched controls, we found that although the risk of developing cancer among FAP patients has been reduced by 50% over the last forty years, that risk is still significantly higher than for matched controls. Colorectal, pancreatic, and duodenal/small bowel cancer, as well as development of second primary cancers, are the main contributors to this increased risk. The risk of gastric cancer did not differ between FAP patients and controls. These findings should be included in future surveillance protocols and treatment guidelines for FAP patients.

References

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.
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.
Karstensen JG, Bulow S, Burisch J, et al. Validation of the Endoscopic Part of the Spigelman Classification for Evaluating Duodenal Adenomatosis in Familial Adenomatous Polyposis: A Prospective Study of Interrater and Intrarater Reliability. Am J Gastroenterol 2022;117(2):343-45.
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.

Disclosure

JGK is a consultant for SNIPR BIOME.