Transcript Direct-To-Consumer Genetic Testing - GEC-KO

Direct-To-Consumer Genetic Testing
Developed by Dr. Judith Allanson, Ms. Shawna Morrison and Dr. June Carroll
Last updated November 2015
Disclaimer
• This presentation is for educational purposes only and should
not be used as a substitute for clinical judgement. GEC-KO
aims to aid the practicing clinician by providing informed
opinions regarding genetic services that have been developed
in a rigorous and evidence-based manner. Physicians must use
their own clinical judgement in addition to published articles
and the information presented herein. GEC-KO assumes no
responsibility or liability resulting from the use of information
contained herein.
Objectives
• Following this session the learner will be able to:
– Refer to their local genetics centre and/or order genetic
testing appropriately regarding direct-to-consumer genetic
testing (DTC GT)
– Discuss and address patient concerns regarding DTC GT
– Find high quality genomics educational resources
appropriate for primary care
Case 1: Jenny
• Jenny, 33yo female in good health
• 6 months ago she found out that her paternal
aunt, who is dying from ovarian cancer, was
found to carry a mutation in the BRCA1 gene
• She didn’t feel this was the best time to approach
the family to inquire further, so she purchased a
DTC-GT kit online which tests the BRCA1 gene
with the hope of being proactive, like Angelina
Jolie
Case 2: Clark
• Clark, 50yo male in
good health
• Recently purchased
a DTC-GT kit out of
curiosity after
reading a news
article
d.85
d.87
MI
90
arthritis
88
86
80
75
AD IDDM
dx 80
50
A&W
Case 3: Jane and Jack
• Jane and her partner, Jack, are corporate lawyers, both in
excellent health
• Their law firm strongly encourages employees to access
the local executive health centre
• The couple had preconception counselling through the
local executive health centre and purchased a carrier
screening panel (screening for carrier status of 100+
recessive diseases)
• Although genetic counselling is available through this
clinic, Jane always bring her results to review with you
• Neither she nor Jack was a carrier of the same recessive
condition
Case 3: Jane and Jack
• Jane has just delivered a healthy baby boy by
uncomplicated vaginal delivery
• As you commonly do, you anticipate prescribing Jane
a combination codeine and acetaminophen after
birth for episiotomy pain, however you recall Jane
had also had pharmacogenomic testing (her
predicted response to certain medication based on
her genotype)
What is direct-to-consumer genetic
testing?
• Direct-to-consumer genetic testing (DTC-GT),
also referred to as personal genome testing,
refers to genetic testing available for ‘overthe-counter’ purchase without health care
provider involvement
What is direct-to-consumer genetic
testing?
• Companies use data generated from genome-wide association
studies (GWAS)
– These are case-control studies which examine single nucleotide
polymorphisms [SNPs]
– SNPs (pronounced ‘snips’) are the most common type of genetic
variation
– Each SNP represents a difference in a single DNA building block,
a nucleotide
– GWAS compare large groups of individuals (unaffected controls
versus individuals with symptoms of a specific disease) in an
attempt to distinguish between non-harmful changes in the
DNA code and pathogenic, disease-causing/predisposing
changes
What is direct-to-consumer genetic
testing?
• For complex health conditions (e.g. heart disease,
diabetes) and traits (e.g. eye colour) individuals are
generally categorized using SNP data as at increased
risk (higher than average), average, or at decreased
risk (lower than average)
• Pharmacogenomics uses SNP data to assess the
kinetics and dynamics of specific drugs in the hope of
avoiding adverse drug effects and to improve
efficiency
What is direct-to-consumer genetic
testing?
• For Mendelian inherited conditions companies will
look for common gene mutations, generally ethnicity
based
– BRCA1 and BRCA2
• 3 Ashkenazi Jewish founder mutations (5382insC, 185delAG,
6174delT) are generally offered
– CFTR (mutations in this gene cause cystic fibrosis)
• A core panel of 23 mutations is generally offered
What is direct-to-consumer genetic
testing?
• Marketed with the promise of providing:
– Predictive genetic risk assessment for a variety of health
conditions (i.e. diabetes, cancer, obesity)
– Information regarding response to and/or side-effect risk
of certain pharmaceuticals (i.e. clopidogrel, statins)
– Carrier status of single gene disorders (e.g. cystic fibrosis,
Tay Sachs disease)
– Ancestry information and link to relatives
– Medically irrelevant information such as bitter taste
perception, ear wax type, curly hair
Who can obtain direct-to-consumer
genetic testing?
• Generally, direct-to-consumer (DTC) genetic
testing is available online to anyone for a cost
• Genetic testing for DTC genetic testing is
usually performed on a saliva sample
How will direct-to-consumer genetic
testing help you and your patient?
• While there are limited data to support the clinical validity
(ability to predict clinical outcome) and utility (the likelihood of
improving patient outcome), some consumers might benefit
from direct-to-consumer genetic testing as results may:
– Encourage positive behaviour modifications (e.g. increase exercise,
smoking cessation)
– Provide useful information for medication choice and/or dose, or
management
– Provide information to individuals who have no or limited
information about their family history (e.g. an individual who was
adopted)
– Reveal carrier status of a genetic condition that could have
implications for family planning or medical management
Are there harms/limitations of direct-toconsumer genetic testing?
• Caution when interpreting direct-to-consumer (DTC)
genetic testing should be exercised as:
– DTC genetic testing does not take into account numerous
factors important when interpreting genetic test results
such as age, family history, lifestyle (e.g. smoking, obesity)
and other environmental factors that are a significant
contribution to common complex disease development
– Clinical utility of some of reported results is questionable
– Family health history-based risk assessment is still the
gold standard in the initial assessment for heritable
conditions
Are there harms/limitations of direct-toconsumer genetic testing?
• Privacy
• No testing regulation
• Discrepant results between companies, different studies may be used
for result interpretation
• Concerns re downstream testing and costs as result of direct-toconsumer (DTC) results
• Truth in advertising (potential for consumers to be misled about the
benefits versus risks and limitations)
• “misattributed equivalence”
– if a DTC test indicates a lower than average lifetime risk for a certain
condition, when FH indicated a much higher risk, a consumer could be
falsely reassured and not be as vigilant about medical interventions
indicated by FH
– This phenomenon speaks to the need for knowledgeable healthcare
provider involvement in pre- and post-test counselling
Back to case 1: Jenny
• Purchased DTC testing to know her BRCA1 mutation carrier
status
• She receives her results and tells you that she is very relieved
because she does not have a mutation in BRCA1
• What are your next steps?
• Review the report
• DTC-GT testing companies generally only screen for a few
founder mutations
• Need to confirm that Jenny was tested for the familial
mutation – still need the familial mutation report
• If she truly is negative for the familial mutation, this is
reassuring, should still confirm result in a clinical lab
company
Back to case 2: Clark
• Purchased DTC for curiosity
• He brings in his laptop to show
you his results
• He is distraught to learn that he
has an increased genetic risk for
Alzheimer disease, he had thought
that he could stave off the disease
by healthy lifestyle choices
d.85
d.87
MI
90
arthritis
88
86
75
80
AD
dx 80
50
A&W
IDDM
How do you counsel Clark?
• APOE is a susceptibility gene and is not a predictive
test. Thus, individuals with no copies of the e4 allele
still face about a 2x increased lifetime risk of
developing AD if they have a first-degree relative
with AD.
• Regardless of his DTC result, based on Clark’s family
history, his AD risk is about 20-25% because of an
affected FDR (actually higher than the risk estimate)
• He should still continue with his healthy lifestyle as
AD develops from a complex interaction between
genetic and environmental factors
Back to case 3: Jane and Jack
• Jane and her partner, Jack, had preconception
counselling through the local executive health centre
• Jane has just delivered a healthy baby boy by
uncomplicated vaginal delivery
• As you commonly do, you anticipate prescribing Jane a
combination codeine and acetaminophen after birth for
episiotomy pain, however you recall Jane had also had
some pharmacogenomic testing (her predicted response
to certain medication based on her genotype)
Jane’s result
•
•
•
•
Codeine
Gene tested - CYP 2D6
Result - Ultrametabolizer
Functional duplications of CYP 2D6, lead to
enhanced codeine to morphine metabolism
(ultra-rapid metabolism - UM) and associated
adverse events
What action can you take?
• Women who are ultra-rapid metabolizers of codeine
will have significantly higher than normal levels of
morphine in breast milk which could consequently
cause problematic or lethal levels in the newborn.
• It is recommended that analgesics other than
codeine be used by nursing mothers
• See GECKO on the run on Codeine metabolism and
breastfeeding
• Pearls
– Direct-to-consumer (DTC) genetic testing is over-thecounter genetic testing available online to consumers
through private companies
– Generally, results report an individual’s probabilistic risk to
develop a medical condition based on genome wide
association studies (GWAS)
– Interpret DTC results with caution
– Family health history-based risk assessment is still the
gold standard in initial assessment for heritable
conditions
Resources
• See www.geneticseducation.ca for more details and
how to connect to your local genetics centre
• To learn more about Canadian ethnicity-based carrier
screening recommendations see the point of care
tool
• For a recent review on DTC-GT see Scott Roberts et
al. Direct-to-Consumer genetic testing and personal
genomics services: a review of recent empirical
studies. Curr Genet Med Rep. 2013; 1(3): 182–200