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)

Abstract

Heritable factors account for approximately 35% of colorectal cancer (CRC) risk, and almost 30% of the population in the UK have a family history of CRC. The quantification of an individual’s lifetime risk of gastrointestinal cancer may incorporate clinical and molecular data, and depends on accurate phenotypic assessment and genetic diagnosis. In turn this may facilitate targeted risk-reducing interventions, including endoscopic surveillance, preventative surgery and chemoprophylaxis, which provide opportunities for cancer prevention. This guideline is an update from the 2010 British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland (BSG/ACPGBI) guidelines for colorectal screening and surveillance in moderate and high-risk groups; however, this guideline is concerned specifically with people who have increased lifetime risk of CRC due to hereditary factors, including those with Lynch syndrome, polyposis or a family history of CRC. On this occasion we invited the UK Cancer Genetics Group (UKCGG), a subgroup within the British Society of Genetic Medicine (BSGM), as a partner to BSG and ACPGBI in the multidisciplinary guideline development process. We also invited external review through the Delphi process by members of the public as well as the steering committees of the European Hereditary Tumour Group (EHTG) and the European Society of Gastrointestinal Endoscopy (ESGE). A systematic review of 10 189 publications was undertaken to develop 67 evidence and expert opinion-based recommendations for the management of hereditary CRC risk. Ten research recommendations are also prioritised to inform clinical management of people at hereditary CRC risk.

British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland/Public Health England post-polypectomy and post-colorectal cancer resection surveillance guidelines

“…These guidelines do not address surveillance in patients affected by hereditary colorectal syndromes, guidelines for which have also been updated recently16 ; however, care has been taken to ensure consistency, avoid overlap and ensure that all patient cohorts are comprehensively covered by one of these guidelines.…”

Comprehensive Constitutional Genetic and Epigenetic Characterization of Lynch-Like Individuals

“…Individuals with MMR deficient tumors and no identified germline MMR mutations account for more than a half of the cases being assessed at genetic counseling units because of LS suspicion. They encompass a heterogeneous group of patients that may benefit from further stratification after comprehensive (epi)genetic characterization [ 50 ]. By combining the use of variant pathogenicity assessment with ad-hoc designed panel and a global epigenetic characterization, we reclassified 9 of 115 cases as LS, one secondary to a constitutional epimutation.…”

“…Since patients with biallelic mutations in MUTYH were previously discarded in our LLS series [ 19 , 31 ], only three heterozygous MUTYH carriers were found (current study and [ 10 ]). As recommended, the estimated risk for monoallelic MUTYH mutation carriers does not support an earlier initiation of colonoscopy screening [ 50 , 52 ].…”

UKCGG Consensus Group guidelines for the management of patients with constitutional TP53 pathogenic variants

“…20 Therefore, the opinion of the Consensus Group is that there is no sufficient evidence that colorectal cancer risk is increased in LFS and that colonoscopic surveillance should only be considered if there is a family history of colorectal tumours according to recently published guidelines and investigation for other inherited causes of colorectal cancer if appropriate. 21 Regarding annual dermatological review, the group recognised the resource implications for this, and it was felt that this could be undertaken by the patient's general practitioner with a low threshold for referral to dermatology.…”