Colorectal cancer/polyposis genes
SyndromeCancer risk managementReferences
Lynch syndrome
Adenomatous polyposis syndromes
Peutz-Jeghers syndrome
Juvenile polyposis syndrome
PTEN-hamartomatous tumour syndromes
See International and European guidance as advised by InSiGHT, plus UK guidance on endoscopic colorectal surveillance issued by the British Society of Gastroenterology (due for revision).
Guidance on management of Lynch syndrome should be interpreted in the light of gene, gender, age and cancer history, as shown by the Prospective Lynch Syndrome Database at http://www.lscarisk.org/.
The reference databases for interpretation of variants in MSH2, MLH1, MSH6, PMS2, EPCAM, APC, MUTYH, POLD1, POLE and STK11 are provided at http://www.insight-database.org/genes.
As listed under individual condition headings at  https://www.insight-group.org/, including the following:
Vasen et al27
Cairns et al28
Vasen et al25
Møller et al15 29
  • *The Ataxia Telangiectasia guidelines recommend 18-monthly mammography, but where ATM pathogenic variants are identified in the context of a significant family history of breast cancer it is reasonable to offer annual mammography, bringing this into line with CHEK2 mutation carriers who have a similar risk. The guidelines do not give specific recommendations for the c.7271T>G variant so this is pragmatic, based on the evidence indicating this variant confers a much higher risk.

  • †For ATM, CHEK2 and PALB2 consider using BOADICEA to guide risk management.24

  • ‡These recommendations include mammography and/or breast MRI. Given that the risk for CHEK2 c.1100delC is well defined, it is reasonable to offer mammography rather than MRI. There is much weaker evidence for other CHEK2 variants, but it seems reasonable to use the same protocol for these until further data emerge.

  • §These recommendations include mammography and/or breast MRI. As there is good evidence that the PALB2 risk is influenced by other factors such as family history, it would be reasonable to offer BRCA-equivalent surveillance to those women ascertained via family history clinics (where there is a strong family history) but to consider less intense surveillance in those women with no significant family history (eg, an incidental finding).

  • BOADICEA, Breast  and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm; BSO, bilateral salpingo-oophorectomy; NHSBSP, National Health Service Breast Screening Programme; NICE,  National Institute for Health and Care Excellence;  TAH, total abdominal hysterectomy; UK-CGG, UK Cancer Genetics Group.