Wylie Burke MD PhD

1
Using Genetic Information in Health Care

• Wylie Burke MD PhD
• Department of Medical History and Ethics
• University of Washington

2
Health benefit from genetic information - 1

• Genetic testing
• ?
• Identification of genetic condition or
  susceptibility
• ?
• Prognosis
• Clinical management

3
3-year-old boy with weakness and family history
of Duchenne Muscular Dystrophy (DMD)

DMD?
4
Duchenne Muscular DystrophyTesting for Carrier
Status

Carrier?
5
Huntington Disease (HD)

50 chance of having inherited HD
Huntington disease Progressive loss of
neurological function starting in the 40s
6
Balance of risk benefit

• Weighing risks of genetic label...
• Discrimination
• Stigmatization
• Harm from therapy of unproven benefit
• ...against opportunity for prevention

7
Discrimination on the basis of medical
information

• Not limited to genetics
• Asymptomatic person with elevated cholesterol or
  diabetes
• Line between acceptable and unacceptable
  distinctions not well defined

8
Key issue Nature of treatment

• How effective?
• How acceptable?
• How safe?
• How available?

9
Phenylketonuria (PKU)

• Mutation in PKU Gene
• ?
• Loss of capacity to handle
• phenylalanine in diet
• ?
• Mental retardation

10
Newborn screening for PKU

• Mandated screening of all newborns
• ?
• Identification of affected newborns
• ?
• Initiation of phenylalanine-poor diet
• to prevent mental retardation

11
Incidence of 6-mercaptopurine toxicity in
children with leukemia
with toxicity
(JNCI 1999 91 2001)
Thiopurine methyltransferase (TPMT) activity

12
Use of pharmacogenetics to reduce drug toxicity

• Child with leukemia
• ?
• Genetic testing to determine
• Thiopurine methyltransferase
• (TPMT) status
• ?
• Adjust chemotherapy
• if TMPT activity low

13
BRCA1/2 testing in a high risk family
Died young

Ov CA, died in 50s
Br CA, died age 47
Br CA, age 40
14
Dual concerns Confidentiality and appropriate
disclosure of disk

• Confidentiality protection applies to ALL medical
  information
• Sharing information with family members may be
  essential for preventive care

15
Research Subjectfound to have BRCA1 mutation

• I watched my sister go through chemotherapy and
  radiation treatments, and it was terrible.
• I cant sit and wait for that to happen to me.

16
Options to reduce risk in women with BRCA1/2
mutations

• Prophylactic surgery (removal of breast or
  ovaries)
• Early breast cancer screening
• Ovarian cancer screening
• Tamoxifen

17
Problems with options for women with BRCA1/2
mutations

• Uncertainties about benefit
• Some options unacceptable to many women
• Most options involve risk, expense and discomfort

18
Assessing treatment Is it effective?

• Is the treatment successful enough to compensate
  for the genetic label?

19
Is it acceptable?

• Is the treatment painful or drastic?
• Does it provide enough benefit to balance the
  discomfort or body change?

20
Is it safe?

• Does the treatment create new health risks?
• If so, are they small compared to the original
  risk?

21
Is it available?

• Is the treatment costly?
• Is the expertise available?
• Can everyone at risk have access to the benefits
  of treatment?

22
When is a predictive genetic test most useful?

• When preventive measures are available AND
• Inappropriate for people who do not have the
  genetic susceptibility

23
Health benefit from genetic information - 2

• Use of genomics to understand disease processed
• ?
• New strategies for prevention and treatment
• ?
• Apply to all who would benefit

24
Possible future options for breast cancer

• Better preventive medications
• more protective
• fewer risks and side effects
• Vaccine
• Antibiotic for breast cancer

25
Complex Causes of Disease

• Genetics Environment
• Major gene effects Exposures
• Genetic background Diet
• Gene interactions Lifestyle
• Disease

26
Progress in Genomic Research
Safe, effective, inexpensive treatments
Proven effective treatments
Possibly effective treatments
Environmental modifiers
Genotypes conferring susceptibility
0
10
20
40
50
60
27
Oversight of clinical research

• Scientific rationale - is the study
  scientifically sound?
• Protection of human subjects
• Contacting potential subjects
• Informed consent process
• Safety monitoring

28
Achieving benefit without harm

• the great question, which still divides medical
  opinion, is do the risks counterbalance the
  advantages..?
• (Anesthesia debate, mid-1800s)