Uptake of Cascade Genetic Testing in Hereditary Pheochromocytoma/Paraganglioma Syndromes

Presentation Number: OR04-1
Date of Presentation: April 1st, 2017

Elisabeth Joye Petr*, Erika Koeppe, Jenae M Osborne, Michelle Jacobs, Kristen Hanson, Monica Marvin, Jessica Everett, Elena M Stoffel and Tobias Else
University of Michigan, Ann Arbor, MI

Abstract

Cascade genetic testing, or the genetic testing of relatives of pathogenic mutation carriers, provides an efficient mechanism to identify individuals at risk for tumor development who may benefit from screening procedures. “Uptake” or participation in cascade genetic testing varies in different inherited conditions. Prior reports suggest that 1-2 relatives of affected individuals with common inherited cancer syndromes such as Lynch syndrome or Hereditary Breast and Ovarian Cancer syndrome complete genetic testing. We investigated the uptake of genetic testing in families with Hereditary Pheochromocytoma (PCC)/Paraganglioma (PGL) syndromes.

We reviewed genetic testing records of patients evaluated at a large academic medical center from 2005-2015. We estimated the number of at-risk relatives tested per positive proband by the proxy measure of ratio of number of site-specific genetic tests ordered over the total number of positive tests resulting from comprehensive full gene analysis.

A total of 91 individuals were found to carry mutations in SDHx, VHL, RET, NF1, TMEM127 and MAX by full gene sequencing analyses and 211 additional individuals had site-specific genetic tests, resulting in 2.3 tested relatives per index patient with a Hereditary PCC/PGL syndrome. Uptake of cascade testing varied by syndrome. For SDHx, a total of 50 positive full sequence analyses and 152 total site-specific tests were performed, resulting in 3 relatives tested per index carrier. For MEN2, a total of 10 positive full sequence analyses and 23 site-specific tests were performed, resulting in 2.3 relatives tested per index carrier. For VHL, a total of 28 positive full sequence analyses and 34 total site-specific tests were performed, resulting in 1.2 relatives tested per index carrier. Overall uptake of genetic testing in families with PCC/PGL related syndromes was 2.3 relatives tested per index mutation carrier, a rate similar to that observed in families with Lynch syndrome (2.2) and Li-Fraumeni syndrome (2.1), and higher than in families with Familial Adenomatous Polyposis (1.6), Hereditary Leiomyomatosis and Renal Cell Cancer (0.6), Birt-Hogg-Dubé syndrome (1.1), and Cowden’s disease (0.7).

We found that uptake of predictive genetic testing was higher in PCC/PGL families, especially those with SDHx mutations, compared to other hereditary cancer syndromes. Patient education regarding the benefits of asymptomatic screening for PCC/PGL and prompt access to genetic testing coordinated through a specialized Endocrine Oncology Clinic likely played a role. However, despite increased availability of genetic testing, the number of tested relatives per index patient remains suboptimal. These data highlight the importance of determining factors that influence the decision of family members to undergo genetic testing in order to increase the detection of genetic mutation carriers.

 

Nothing to Disclose: EJP, EK, JMO, MJ, KH, MM, JE, EMS, TE