Objectives: The MYH gene has recently been associated with multiple colorectal tumours. It participates in the DNA base-excision-repair, avoiding mutations in other genes, namely the APC and Ki-ras. Recently, biallelic MYH mutations have been described in patients with attenuated polyposis and in 7.5% with classic polyposis and no detectable APC mutation. The aim of this study was to analyse the incidence of germ-line MYH mutations in selected Portuguese families recorded in a hereditary tumour registry and to evaluate the risk of colorectal cancer in this syndrome.
Patients and methods: Nineteen APC mutation negative patients, 13 presenting attenuated polyposis and 6 with classic familial adenomatous polyposis (> 100 adenomas), were screened for germline biallelic MYH mutations.
Results: Biallelic germline mutations in MYH were identified in 9 of the attenuated polyposis and in one of the classic polyposis patients. The mean age at the clinical diagnosis was 50.6 years (from 35 to 69 years); six were men and four women. Five patients belonged to families with affected siblings; three showed evidence for vertical transmission and two had no evidence for familial transmission of the disease. No extra-colonic manifestations were reported. All patients had surgical resections: five total colectomies, four reconstructive proctocolectomies and one left hemicolectomy. Eight patients had associated malignant degeneration: three T3N+, four T3N0 and one T1N+. In the follow-up two patients died due to tumour recurrence.
Conclusion: A large frequency of biallelic MYH mutations (69%) was found in APC mutation negative patients belonging to families with attenuated polyposis; the highest percentage was observed in families presenting evidence for horizontal transmission of the disease. The high percentage of degeneration found in these patients suggests that colonoscopy with polypectomies is not sufficient and prophylactic colectomy is recommended. The identification of MYH associated polyposis is important to evaluate the level of risk, particularly for the siblings.