OR11: Risk factors for the presence of pathogenic APC and biallelic MUTYH mutations in patients with multiple adenomas

Nielsen1, S.W. ten Broeke1, S.S. Badal1., T. van Wezel2, H. Morreau2, FJ. Hes1, H.F. Vasen3,4, C.M. Tops1.

This study was supported by the Dutch Cancer Society

1 – Department of Clinical Genetics, Leiden University Medical Centre, the Netherlands. 2 – Department of Pathology, Leiden University Medical Centre, the Netherlands. 3 – The Netherlands Foundation for the Detection of Hereditary Tumours, Leiden, the Netherlands, 4 – Department of Gastroenterology, Leiden University Medical Centre.


Patients with multiple colorectal adenomas may carry germline mutations in APC or MUTYH, but mutation detection rate seems to be declining. The aims of this study were (1) to assess the proportion of these mutations in patients with multiple adenomas and (2) to identify risk factors that predict mutation detection.


We performed mutation analysis of APC and/or MUTYH in a Dutch cohort of 1933 patients ascertained from family cancer clinics between 1992 and 2015. Risk factors were examined using (multinomial) logistic regression analyses.


The overall detection rate declined from 54% before to 14% after 2004. The proportion of APC/MUTYH carriers in patients with <20 polyps was low (3.5%;25/722). Only one mutation was identified in the patient group (n=198) of 10-19 adenomas diagnosed at age 60<. A younger age at adenoma diagnosis and a first degree relative (FDR) with polyps was associated with higher odds of finding an APC mutation, but CRC in a FDR was not. Having CRC was only predictive of finding biallelic MUTYH mutations.


Adenoma count and younger age at adenoma detection are the main predictive factors of finding a mutation, but a FDR with CRC is not. For patients over age 60 with less than 20 adenomas testing does not seem justifiable. Our findings have an important impact on referral policy.