154P - Genetic characteristics of participants in the Australian Pancreatic Screening Study

Background

The Australian Pancreatic Screening study offers endoscopic ultrasound surveillance for individuals at increased risk of developing pancreatic cancer. Given 5-10% of pancreatic cancers are linked to genetic predisposition, all participants are required to undergo genetic counselling. We report on the genetic characteristics of this initial cohort from our institution.

Methods

This is a multicentre, prospective cohort study. Individuals with 2 or more family members with pancreatic cancer (including one of first-degree association) and/or those with a known genetic syndrome were defined as high-risk and eligible for study entry. Subjects aged between 40 and 80 years (or 10 years younger than the relative with pancreatic cancer) were included. The study was approved by the Austin Health Human Research Ethics Committee and the first participant consented in July 2013. Data was collected through participant completed questionnaires and review of medical records. All participants were seen by a Familial Cancer Clinic. Those with an indication for further genetic testing were offered gene panel tests. Indications that there may be an inherited predisposition to pancreatic cancer includes; a family history of breast and ovarian cancer, bowel cancer, melanoma, and chronic pancreatitis.

Results

121 participants were recruited from 96 families. In 12 out of 96 families there was a previously known high-risk germline mutation (6 BRCA2, 3 CDKN2A, 2 PALB2 and 1 STK11). 12 out of 84 families with no known mutation were offered genetic testing, either clinic or self-funded and 8 proceeded. Germline pathogenic mutations (Class 4 or 5) were detected in 3/8 families (37.5%), making the overall pick-up rate 3/84 (3.6%). Two families had a BRCA2 mutation and the other a CDKN2A mutation. In one family, where a pathogenic BRCA2 gene mutation was identified, cascade testing identified a further 3 relatives who carried the BRCA2 mutation. The CDKN2A carrier had a significant personal and family history of cutaneous melanoma. 1 participant had a PALB2 variant of uncertain significance.

Conclusions

In an enriched population, based on pedigree and increased genetic susceptibility, the rate of germ line mutations was high. Gene panels should be considered in selected patients undergoing high risk screening.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

National Health and Medical Research Council.

Disclosure

All authors have declared no conflicts of interest.