Hereditary colorectal, gastric, and pancreatic cancer: comprehensive review

Abstract

Background: Inheritance patterns show familial clustering of gastrointestinal cancers, and multiple germline conditions have now been identified that predispose to colorectal, gastric, and pancreatic cancers.

Methods: A narrative review based on recent relevant literature was conducted.

Results: Lynch syndrome, formerly known as hereditary non-polyposis colorectal cancer, increases the risk of several abdominal cancers, with the highest population prevalence. Familial adenomatous polyposis and some of the more infrequent polyposis syndromes have distinct characteristics affecting various organ-specific cancer risks. Hereditary gastric and pancreatic cancer syndromes include those also causing colorectal cancer, while additional genetic disorders predisposing only to upper gastrointestinal malignancies have been recognized more recently. Diagnosing and managing hereditary cancer syndromes requires multidisciplinary expertise and may be best managed in tertiary centres, with a need to consider patient preference and ensure shared decision-making.

Conclusion: Several germline conditions predispose to colorectal, gastric, and pancreatic cancer, which inform identification, surveillance regimens, prevention, cascade screening, counselling, and surgical management. The authors describe developments in the hereditary origin of colorectal, gastric, and pancreatic cancer with current recommendations in surveillance and surgical management.

Fig. 1

Surveillance recommendations for individuals with a family history of CRC CRC, colorectal cancer; FDR, first-degree relative. Modified from British Society of Gastroenterology recommendations.

Fig. 2

Classification of CRC syndromes MMR, mismatch repair; CRC, colorectal cancer; FAP, familial adenomatous polyposis; aFAP, attenuated familial adenomatous polyposis; PPAP, POLE/POLD1- associated polyposis; MAP, MUTYH-associated polyposis; CMMRD, constitutional mismatch repair deficiency; PJS, Peutz–Jeghers syndrome; JPS, juvenile polyposis syndrome; PHTS, PTEN hamartoma tumour syndrome. Modified from Daca Alvarez et al. and Valle et al.