Dedicated Clinics: Referrals on the basis of family history are best coordinated through centres with a specialist interest, such as regional genetics services or medical/surgical gastroenterology centres. Such centralisation enables audit of family history ascertainment, assigned level of risk, collection of outcome data and research.
Screening Procedure: Total colonoscopy is the preferred mode of surveillance for the moderate risk categories defined here, owing to the propensity for proximal colonic lesions and the opportunity for snare polypectomy. Incomplete colonoscopy should initiate an alternative imaging modality on the same day, such as double-contrast barium enema or CT colonography. A repeat colonoscopy soon after an incomplete examination is acceptable, but success must be assured. However, radiation exposure should be minimised and regular radiological surveillance is not recommended.
High moderate risk group inclusion criteria comprise familial aggregations where affected relatives are first-degree relatives of each other (first-degree kinship) with at least one being a first-degree relative of the consultand. If both parents are affected, these count as being within first-degree kinship:
– Three affected relatives any age in a first-degree kinship (eg, a parent and a blood-related aunt/uncle and/or grandparent), at least one of whom is a first-degree relative of the consultand, or two siblings/one parent or two siblings/one offspring combinations, or both parents and one sibling. However, there should be no affected relative <50 years old, as otherwise the family would fulfil high risk criteria.
– Two affected relatives aged <60 years in a first-degree kinship or mean age of two affected relatives <60 years. At least one relative must be a first-degree relative of the consultand and so this category includes a parent and grandparent, >2 siblings, >2 children or child+sibling. The risk is sufficiently increased to merit low-intensity surveillance comprising 5-yearly colonoscopy between age 50 and age 75 years. Polyps should be snared; adenoma surveillance applies thereafter if a benign neoplasm is confirmed.
Low-moderate risk group. Inclusion criteria are:
– One affected first-degree relative under 50 years old or
– Two affected first-degree relatives, aged 60 or older.
In both high-moderate and low-moderate categories, pathology tumour material from an affected relative may be available to test for Lynch syndrome gene involvement.
Excluding such instances, there is a modest excess risk meriting a single colonoscopy at age 55 (if older at presentation then instigate forthwith), in the low–moderate group to identify polyp formers. Polyps should be snared; adenoma surveillance applies thereafter if a benign neoplasm is confirmed. If colonoscopy is clear, reassure and discharge with recommendations relevant to population risk (uptake of faecal occult blood test screening in the UK).
Early-onset colorectal cancer (<50 years). The elevation of risk in relatives of an early-onset case is modest. However, the heightened anxiety and emotive nature of cancer in this age group merit special mention because this frequently initiates requests for surveillance. Such cases are covered by the above risk categorisation, but algorithms can also be used to predict whether the affected relative is a carrier of a mutation in a Lynch syndrome gene. These approaches identify affected individuals where tumour immunohistochemistry and/or microsatellite instability analysis could lead to identification of a DNA mismatch repair gene mutation. Bethesda criteria are not discriminatory within this group because all patients fulfil these criteria due to age alone.
Low Risk Group: People with only one affected relative and who do not fulfil any of the above criteria, and do not fulfil high risk criteria, should be reassured and encouraged to avail themselves of population-based screening measures. The low level residual risk over that of the general population should be explained.
Outcome of screening in Moderate Risk Groups (Dove-Edwin et al BMJ 2005)
Colonoscopic surveillance is effective in preventing colorectal cancer in individuals from families with hereditary non-polyposis colorectal cancer (group 4) and in individuals with a family history of colorectal cancer that does not meet the Amsterdam criteria. However, colonoscopic surveillance in the families at moderate risk seems not indicated until age 45 (or even 50), and this is true even for the relatives of young patients. Furthermore, surveillance intervals of more than five years may be appropriate in individuals with a moderate risk family history (groups 1-3) in whom no advanced pathology is found.
Colonoscopic polypectomy has been shown to decrease the incidence of colorectal cancer in a large cohort study as well as in clinical practice and to decrease both the incidence and mortality of colorectal cancer in individuals with a family history of hereditary non-polyposis colorectal cancer. It is also considered by some to be a safe tool for population screening. Clear guidelines exist for colorectal surveillance in hereditary non-polyposis colorectal cancer families, but guidelines and practices for individuals at moderate risk on the basis of their family history are heterogeneou.
Concerns exist about colonoscopic surveillance in individuals with a moderate risk family history, as some will not be at increased risk. Dunlop et al calculated that if surveillance were offered to individuals aged 30-70 who have two direct relatives affected or one under age 45 then 235 000 individuals would be eligible in the United Kingdom. Even if the age of initiating surveillance is raised, the potential burden on resources is immense. Colonoscopy is associated with a small risk of serious complications, and this may substantially outweigh any benefits in people at low risk.
In this study, only one incident cancer was detected on surveillance in an individual with a moderate risk family history during 9281 person years of follow-up. In families at moderate risk, advanced neoplasia is very rare below the age of 45 and, if not seen initially, it remains uncommon (under age 65) if follow-up colonoscopy is carried out within six years. These findings are important because individuals with a moderate risk family history who are under age 65 with no advanced neoplasia can be considered to be at low risk and extended surveillance intervals may be sufficient. Individuals with a moderate risk family history in whom advanced neoplasia is seen on initial colonoscopy should continue with colonoscopy every three years. The low yield of advanced neoplasia under the age of 45 is true also of those with a first degree relative affected under age 45. Only 4% of 139 individuals in group 1—families with one case of colorectal cancer diagnosed under age 45, and no other cases—screened under age 45 (mean age 33) had an adenoma of any description. Despite the increased risk of colorectal cancer in this group individuals’ absolute risk therefore remains small and the benefit of screening seems minimal below the age of 45.
- Metachronous colorectal cancer risk in patients with a moderate family history – KF – Colorectal Disease – Wiley Online Library (familyhistorybowelcancer.wordpress.com)
- Lynch Syndrome (familyhistorybowelcancer.wordpress.com)
- Missing Follow-Up Colonoscopies Could Raise Colon Cancer Risk (nlm.nih.gov)
- Hereditary Colorectal Cancer Syndromes (familyhistorybowelcancer.wordpress.com)
- Information for GPs https://familyhistorybowelcancer.wordpress.com/2012/08/11/information-for-gps/