Transcript Characteristics of Genetic Data

Characteristics Of Genetic Data
Joann Boughman, Ph.D.
[email protected]
Characteristics of Genetic Data
Genetic Data is:
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Personal
Permanent
Predictive
Prejudicial
Pedigree-sensitive
Context and Implications
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MEDICAL
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ETHICAL, LEGAL & SOCIAL (ELSI)
Definition of ‘Genetic Test’
Genetic test – An analysis of
chromosomes, genes, and/or gene
products to determine whether a
genetic variation related to a specific
disease or condition is present
Types of Genetic Tests
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Diagnostic testing
Newborn screening
Carrier testing
Prenatal testing
Predictive testing
Diagnostic Testing
Diagnostic testing is used to confirm or
rule out a known or suspected genetic
disorder in a symptomatic individual.
May help: as an adjunctive test
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in making a prognosis
in treatment choice
in planning/intervention strategies
determine risk to relatives
Healthcare Practitioners Already Use
Genetic Tests in General Medical Care
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41yo male with chest pain in ER
father & paternal uncle had MI’s at 40 and 44
information alters admission decision and f/u
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3yo female with delayed speech, slow
reaction
abnormal audiogram, Connexin 26 mutation
GENETIC INFORMATION IS POWERFUL
Newborn Screening
Mandatory testing to detect cases at birth
(i.e., as soon as possible)
Diagnosis:
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PKU
MSUD
galactosemia
congenital hypothroidism
sickle cell disease
homocystinuria
biotinidase
congenital adrenal hyperplasia
Next
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Steps:
Intervention
Follow-up,
treatment and
prevention
Carrier Screening
 Recessive,
monogenic disorders
cystic fibrosis
hemophilia
 Selected
(at-risk) population
Tay-Sachs disease
Sickle cell disease
Carrier Test Results
 Definition
of “negative” or “noncarrier” complicated by multiple
allelic mutations
 Definition
of “positive” only fully
understood by patient when put in
context of risk to offspring
Prenatal Testing
Reasons for Testing:
To assess health of fetus, often when
pregnancy is at increased risk of a genetic
condition depending on the mother’s:
- maternal age
- family history
- ethnicity
- suggestive multiple marker screen
- fetal ultrasound
Predictive Testing
 Offered
to asymptomatic individuals
with increased risk of a genetic
disorder (i.e. with a family history of
the disorder)
– Presymptomatic: eventual development of the
disorder is certain if mutation is present
– Predispositional: eventual development of
symptoms is likely but not certain in presence
of mutation
Predictive Testing
Predictions are tricky…………
especially ones about the future.
Yogi Berra
Predictive Genetic Tests (PGT)
How do they differ from other medical tests?
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Give information about the “future” in
addition to the present condition
Will results of test affect other relatives?
(Is info pedigree sensitive?)
- some choose not to test
- recognized risks to offspring
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Results are complex and probabilistic
- definitions of negative and positive results
and their impact on the patient and family
Some Common Diseases with a
Known Genetic Component
DM I/II
 Cancer(s)
 CVD
 Glaucoma
 Alzheimer
 Schizophrenia
 Bipolar disease
 Head trauma outcome
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HNPCC Clinical Features
Accounts for 5-10% of “sporadic” colon
cancer cases
 Early but variable age at CRC diagnosis
(~45)
 Tumor site in proximal colon predominate
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Associated extracolonic cancers:
endometrium, ovary, stomach, urinary tract,
small bowel, bile ducts, sebaceous skin tumors
Familial Risk for Colorectal Cancer
100
70%
80
Approximate
lifetime
CRC risk
(%)
60
40
20
0
2%
6%
None One 1°
8%
10%
17%
One 1° One 1° Two 1°
and two
age
2°
<45
HNPCC
mutation
Affected family members
Aarnio M et al. Int J Cancer 64:430, 1995
Houlston RS et al. Br Med J 301:366, 1990
St John DJ et al. Ann Intern Med 118:785, 1993
ASCO
Pedigree S.H.
colon cancer
colon and uterine cancer
ovarian cancer
died @ 22
colon @ 50, uterine @ 52
colon @40
uterine @ 44
Ovarian @ 44
died at 22
Cancer Risks in HNPCC
100
% with 80
cancer
60
Colorectal 78%
Endometrial 43%
40
Stomach 19%
Biliary tract 18%
Urinary tract 10%
Ovarian 9%
20
0
0
20
40
60
80
Age (years)
Aarnio M et al. Int J Cancer 64:430, 1995
ASCO
Surveillance Reduces Risk of
Colorectal Cancer in HNPCC
30
No surveillance
Surveillance
% of
subjects 20
with CRC
11.9%
10
4.5%
0
0
3
6
Years of follow-up
Jarvinen HJ et al. Gastro 108:1405, 1995
9
ASCO
Other Predictive Scenarios
 Breast
Cancer
– BRCA1
– BRCA2
 Diabetes
– Type I versus Type II
 Alzheimer
– ApoE
Disease
Problems with Predictive Testing
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Analytical sensitivity
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Clinical validity and utility
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Complexity of interpreting results
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Challenge of assuring patient understanding
– Need informed consent?
– Transmission of results
– Translation of results
Potential Harms of Genetic Testing
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Knowledge can cause (undue) anxiety
- especially if considered deterministic
Family relationships may be disrupted
- when results are shared
- when results are not shared
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Possible misuses of genetic information
- insurance discrimination
- employment discrimination
- social stigmatization
Balance of Value vs. Potential Harms
Healthcare practice must change as new
treatments are introduced
 Adjust if preventions are available AND used
 Depends on the individual and the context
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- Ability to utilize information
- Family situation
- Reproductive options
 This
balance will improve with increased
public understanding of genetics
Genetic Information is:
 Personal
 Permanent
 Predictive
 Prejudicial
 Pedigree-sensitive
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POWERFUL