Highlights
- •Due to limits in Ontario’s genetic testing criteria, we tested first-degree relatives of deceased ovarian cancer patients.
- •Pathogenic variants were found in 10% of participants; rates were highest when a relative was diagnosed prior to age 60.
- •All participants discussed results with their relatives and engaged in enhanced screening or risk reduction.
- •Our findings support changing genetic testing guidelines in Ontario and provide a framework to notify eligible individuals.
Abstract
Background
Up to 20% of high-grade serous ovarian carcinomas (HGSOC) are hereditary; however,
historical uptake of genetic testing is low. We used a unique combination of approaches
to identify women in Ontario, Canada, with a first-degree relative (FDR) who died
from HGSOC without prior genetic testing, and offer them multi-gene panel testing.
Methods
From May 2015-Sept 2019, genetic counseling and testing was provided to eligible participants.
Two recruitment strategies were employed, including self-identification in response
to an outreach campaign and direct targeting of FDRs of deceased HGSOC patients treated
at our institution. The rate of pathogenic variants (PV) in established/potential
ovarian cancer risk genes and the benefits/challenges of each approach were assessed.
Results
A total of 564 women enrolled in response to our outreach campaign (n = 473) or direct recruitment (n = 91). Mean age at consent was 52 years and 96% did not meet provincial testing criteria.
Genetic results were provided to 528 individuals from 458 families. The rate of PVs
in ovarian cancer risk genes was highest when FDRs were diagnosed with HGSOC <60 years
(9.4% vs. 3.9% ≥ 60y, p = 0.0160). Participants in the outreach vs. direct recruitment cohort had a similar
rate of PVs; however, uptake of genetic testing (97% vs. 89%; p = 0.0036) and study completion (95% vs. 87%; p = 0.0062) rates were higher in the former. Eleven participants with pathogenic variants
have completed risk-reducing gynecologic surgery, with one stage I HGSOC and two breast
cancers identified.
Conclusion
Overall PV rates in this large cohort were lower than expected; however, we provide
evidence that genetic testing criteria in Ontario should include individuals with
a deceased FDR diagnosed with HGSOC <60 years of age.
Keywords
Abbrevations:
FDR (first-degree relative), GC (genetic counseling), HGSOC (high-grade serous ovarian cancer), NOK (next-of-kin), PV (pathogenic variant), RRSO (risk-reducing salpingo-oophorectomy), UHN (University Health Network), VUS (variant of uncertain significance)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: April 13, 2021
Accepted:
April 9,
2021
Received:
February 5,
2021
Identification
Copyright
© 2021 Elsevier Inc. All rights reserved.
