P20: Characterization of the clinical phenotype associated with the POLD1-Leu474Pro mutation

Ester Martín Tomás1, Adela Castillejo2, Eva Hernández Illán3, María Isabel Castillejo2, Beatriz Sánchez Heras4, José Luis Soto2.

1 – Análisis Clínicos. Hospital Universitario Elche, Spain. 2 – Genética Molecular. Hospital Universitario Elche, Spain. 3 – Unidad Investigación. Hospital Universitario Alicante, Spain. 4 – Consejo Genético en Cáncer. Hospital Universitario Elche, Spain.

On behalf of the Hereditary Cancer Program of the Valencian Region


We aimed to explore the clinical phenotype associated with a specific POLD1 mutation found in the Valencian Region, in order to propose an appropriate surveillance program to these families.


Three apparent unrelated families carrying the POLD1_Leu474Pro mutation were included in this study. Clinical and molecular data from members of these families were collected. Penetrance estimates as global and stratified by age and sex was calculated. Analysis of the clinical expressivity in carrier individuals was also approached.


We collected data from 24 genetically tested individuals from the only three families reported to date with the POLD1_Leu474Pro mutation (16 carriers and 8 non-carriers). Eleven tumours diagnosed in eight carrier patients (6 CRC, 3 endometrial cancers, a small bowel tumour and an esophageal tumour) and oligopolyposis (<= 3 adenomas) in another two patients were considered. The median age of cancer onset for all POLD1 mutation carriers was 46 years (23-58 years). The observed penetrance was 50% (40% in males and 54.6% in females). The cumulative risk of cancer at age of 50 was 38.5%.


The clinical phenotype for this mutation is similar to that in Lynch syndrome and consequently, the recommended surveillance might be similar.  Phenotype´s analysis by specific mutations might offer more accurate predictive information.