Personalized Medicine in the Era of Genomics

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Personalized Medicine in the Era of Genomics
Wylie Burke MD PhD
Department of Medical History and Ethics Center
for Genomics and Healthcare Equality University
of Washington
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Personalized medicineOne view

• The right treatment, for the right patient, at
  the right time

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Personalized medicineAnother view

• Attending to the whole person, in context of
  personal medical history and life circumstances
• Safran 2003 Ann Intern Med 138248
• Working alliance of doctor patient
• Agreement on goals of treatment
• Collaboration
• Liking and trust
• Fuertes et al 2006 Pat Ed Counsel 6629

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Newborn screening for PKU

• Screen for newborn for elevated phenylanaine
• ?
• Identify affected newborns
• ?
• Diet to prevent mental retardation

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Personalized care for children with PKU

• Cost of diet
• Social barriers to maintaining diet
• Childs commitment to lifetime diet

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Pathways from genetic research to clinical
benefit
Testing to diagnose or identify risk

• Research
• on genetics
• disease

Improved disease classification
Innovative therapy
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Medullary thyroid cancer RET mutation
testingMultiple Endocrine Neoplasia 2 (MEN2)
Medullary thyroid cancer
Medullary thyroid cancer, RET mutation
If RET , offer prophylactic thyroidectomy
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Predicting toxicity from chemotherapy
Retrospective analysis of clinical trial data
with toxicity in children with leukemia
JNCI 1999 91 2001
Thiopurine methyltransferase (TPMT) activity

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Pathway from test to benefit
ACTION
Health benefit

• Test

Result
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Spectrum of genetic contribution to disease
Genes and Environment
Mostly Environment
Mostly Genetic
Cystic fibrosis
Diabetes Asthma
Chicken pox
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Gene variants associated with common complex
diseases

• Low relative risk (most lt2.0)
• Polygenic
• Often account for only a small percentage of
  disease cases

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Multiple contributors to asthma

• Genetics
  Environment
• -beta-adrenergic -mites
• receptor -cockroaches,
• -GSTM1, GSTT1 -pollens
• -IL-4, IL-4RA, IL-13 -animal danders,
• -TNF-alpha -cigarette smoke,
• -30-50 others -diesel fuel
• Asthma

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Can genetic test results provide a threshold for
clinical intervention?
ACTION
Improved outcome

• Genetic test

USUAL CARE
No reduction in outcome
-
or NO ACTION
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Estimate of lifetime diabetes risk Based on
presence/absence of disease-associated mutation

Janssens Khoury, It J Pub Health 2005 335-41

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Risk of age-related macular degeneration Effect
of population variation in 3 genes
1 have gt 50 risk of AMD MOST have risk close
to average
Nat Genet 2006 381055-9
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Data gaps

• Often not known
• Whether testing leads to improved health outcome
• Whether testing influences management decisions
• Whether testing is associated with direct or
  indirect harms

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Policy questions if benefit is present

• Does the benefit outweigh potential harms?
• Who participates in decisions about appropriate
  use?
• How is equitable access assured?

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Guiding principle

• (After Osler)
• More important to know the patient who has the
  genotype than the genotype that has the patient