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Barriers and facilitating factors for
implementation of genetic services
Martina Cornel
Professor of Community Genetics and Public Health Genomics
VU University Medical Center, Amsterdam
EUPHA 11 November 2016
Round table "Bridging the gap between knowledge and practice in
public health genomics"
The PRECeDI project has received funding from the European Union’s Horizon 2020
research and innovation programme under grant agreement No 645740.
Role in the Project – Domain 4
2000: genome sequence published
Bill Clinton: We are here to celebrate the completion of the
first survey of the entire human genome …
With this profound new knowledge, humankind is on the
verge of gaining immense, new power to heal. Genome
science will have a real impact on all our lives -- and even
more, on the lives of our children.
It will revolutionize
the diagnosis, prevention
and treatment of most,
if not all, human diseases.
Collins FS (Right at photo). Nature 2010 &
© AP PHOTO/RON EDMONDS
http://www.genome.gov/images/content/cost_per_megabase2.jpg
Collins, 10 years later (Nature 2010;464:674-5)
Has the revolution arrived?
The consequences for clinical medicine, however, have
thus far been modest.
Those who somehow expected dramatic results overnight
may be disappointed, but should remember that
genomics obeys the First Law of Technology:
we invariably overestimate the short-term impacts of
new technologies and underestimate their longer-term
effects.
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What to prioritize?
considerations of medical benefit, health need and costs
• evidence of benefit in terms of clinical benefit,
• benefit of information for important life decisions,
• benefit for other people apart from the person tested
and the patient specific likelihood of being affected by
the condition tested for
Severin et al. European Journal of Human Genetics (2015) 23, 729–735
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Barriers?
• Lack of genetic knowledge relevant for every day
care in other sectors of medicine
• Lack of HTA for application of genetics
• Lack of translational research in terms of
translation “from bench to bedside” (unlike
translational research “from mice to man”)
– How to integrate in daily practice?
– Guidelines, funding, access, programmatic approach
• Commercial offers direct-to-consumers (DTC) of
tests with low predictive value – undermining
trust
What to prioritize… criteria?
Penetrance
The likelihood of symptoms in a person with the mutation
High predictive value
60-80% breastcancer risk in
BRCA1&2 (lifetime risk)
Interventions available
Oöphorectomy,
Mammography or mastectomy
Clinical utility
More healthy years
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Figure: Hartman 2016 NEJM
What to prioritize… criteria?
1. Breast cancer in the family at a young age
2. Potentially high risk
3. Interventions available
"I CARRY A “FAULTY” GENE, BRCA1, WHICH SHARPLY
INCREASES MY RISK OF DEVELOPING BREAST
CANCER AND OVARIAN CANCER. [...] ONCE I KNEW
THAT THIS WAS MY REALITY, I DECIDED TO BE
PROACTIVE AND TO MINIMIZE THE RISK AS MUCH I
COULD. I MADE A DECISION TO HAVE A PREVENTIVE
DOUBLE MASTECTOMY. I STARTED WITH THE
BREASTS, AS MY RISK OF BREAST CANCER IS
HIGHER THAN MY RISK OF OVARIAN CANCER, AND
THE SURGERY IS MORE COMPLEX. [...] I CAN TELL MY
CHILDREN THAT THEY DON’T NEED TO FEAR THEY
WILL LOSE ME TO BREAST CANCER."
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Colon cancer?
• FAP, Lynch (HNPCC)
• Colonoscopy
• Aspirine decreases cancer
risk in Lynch syndrome
(CAPP3 trial)
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Screening? Cascade screening!
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Screening? Cascade screening!
father
brother
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Beyond BRCA and Lynch
• Cardiogenetics
– LQTS, HCM, ARVC/ARVD, etc
• Oncogenetics
–
–
–
–
© Lectrr Borry Matthijs
BRCA 1&2
Lynch syndrome (hereditary non-polyposis colorectal cancer)
Familial adenomatous polyposis
multiple endocrine neoplasia (MEN1, MEN2A, MEN2B, …)
• Diabetes
– Monogenic subtypes (MODY) such as
• GCK MODY (mild, but risk of perinatal death)
• HNF1A and HNF4A MODY manage well on a low dose of sulfonylureas
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Service stratified according to profile?
http://www.nature.com/nrg/journal/v17/n7/fig_tab/nrg.2016.27_F2.html
Service stratified according to profile?
http://www.nature.com/nrg/journal/v17/n7/fig_tab/nrg.2016.27_F5.html
Beyond “monogenic”
• Testing increasingly with “(onco)panels” in clinical genetics
services
– BRCA1/2/CHEK2
– 46 “well known” syndromes
– >100 genes if many different cancers
• Which gene(variant) to be added next?
– PALB2 – rare but similar impact as BRCA1/2
– “multifactorial” gene set to tailor breast cancer screening?
•
•
•
•
Some women start at 25 years of age (high risk surveillance)
Some start at 40 years of age (moderate risk surveillance)
Some start at 50 and come only once every 5 years
Some don’t need mammography
• Testing with polygenic risk models? Not yet in services, first
pilots ongoing
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Who takes the initiative?
• Government in Familial Hypercholesterolaemia in The
Netherlands until recently (2013)?
• Public health for national screening programmes?
• Clinical geneticist for family members of index?
• Oncologist for cancer patient?
• Pathologist for MSI testing or immunohistochemistry (Lynch)?
• Primary care physician to inform or alert family members?
• …..
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Public health: work to be done!
• Genetic education
• HTA, prioritization
• Integration of genetics in screening
– Stratification according to risk (genetic & other)
• Collaboration, coordination, attunement
between stakeholders
• Access, funding, programmatic approach
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Conclusion
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