Integrating Genomics into Clinical Practice

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Integrating Genomics into Clinical Practice

• Jan Dorman, PhD
• University of Pittsburgh
• School of Nursing
• jsd_at_pitt.edu

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Applications of Genomics to Clinical Practice

• Molecular diagnosis
• 1000 for human genome sequence
• Prediction of a healthy persons risk of disease
• Including cancer, cardiovascular disease,
  diabetes, etc.
• Evaluation of responses to drugs and
  environmental agents
• Pharmacogenomics

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Where do clinicians begin?

• Begin with assessment of family history
• Even when an individuals genome can be
  displayed on a personal microchip, interpreting
  that information will depend in large part, on
  the biological and environmental contexts in
  which the genome is expressed, and the family
  milieu is as good a guide as any.
• Pyeritz RE. JAMA 278235. 1997

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Family Health History

• Is an important risk factor for chronic diseases
  that reflects
• Inherited genetic susceptibility
• Shared environment risk factors (diet)
• Cultural factors (religious practices)
• Common behaviors (smoking, physical activity)
• Prior to offering any genetic susceptibility
  testing, a clinician needs to assess the family
  history of disease
• Who should be tested?
• What genes should be tested?

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Family History of Diabetes

• T2D is an independent risk factor for the disease
• 88-95 have affected 1st degree relatives
• 70-77 have affected 2nd degree relative
• Individuals with a positive family history are
  about 2-6 times more likely to develop T2D than
  those with a negative family history
• Risk 40 if 1 T2D parent 80 if 2 T2D parents

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Family History of Diabetes

• FH identifies a group of high risk individuals
• Using a simple and inexpensive approach
• Who may benefit from early detection
• To develop personal and family-based risk factor
  modification strategies
• In the future, may benefit from genetic testing
• Has been difficult to find genes for T2D
• Late age at onset
• Polygenic inheritance
• Multiple genes with small effects
• Multifactorial inheritance

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Collecting Family History Information in Clinical
Practice

• Barriers
• Underestimation (by clinicians and patients) of
  value of family history information
• Limited knowledge and training in human genetics
• National Coalition for Health Professional
  Education in Genetics (NCHPEG) endorsed core
  competencies for all health-care professionals in
  2000

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NCHPEG Core Competencies

• Represents minimum knowledge, skills and
  attitudes necessary for health professionals in
  all disciplines to provide patient care that
  involves awareness of genetic issues and concerns
• Medicine - Dentistry
• Nursing - Psychology
• Public Health - Social work

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NCHPEG Core Competencies

• Appreciate limitations of his or her genetic
  expertise
• Understand the social and psychological
  implications of genetics
• Know how and when to make a referral to a genetic
  professional

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Some NCHPEG Recommendations

• Knowledge
• Importance of family history (minimum of 3
  generations) in assessing predisposition to
  disease
• The range of genetic approaches to treatment of
  disease
• Resources available to assist clients seeking
  genetic information
• The indications for genetic testing and / or
  gene-based interventions

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Some NCHPEG Recommendations

• Skills
• Gather genetic FH information, including multiple
  generation pedigrees
• Identify families who would benefit from genetic
  services
• Educate individuals regarding these services, and
  their risks and benefits
• Attitudes
• Appreciate the sensitivity of genetic information
  and the need for privacy and confidentiality
• Demonstrate willingness to update genetics
  knowledge at frequent intervals

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Collecting Family History Information in Clinical
Practice

• Other barriers
• Lack of time
• Lack of reimbursement for collecting the
  information
• Concerns about insurance / employment
  discrimination
• Lack of convenient tools / software for data
  collection

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Family History Tools in the
Popular Literature
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US Surgeon Generals Family History Initiative

• First National Family History Day, Thanksgiving,
  11/25/2004
• US Partners
• Office of the Surgeon General
• National Human Genome Research Institute (NHGRI)
• Centers for Disease Control and Prevention (CDC)
• Agency for Healthcare Research and Quality (AHRQ)
• Health Resources and Services Administration
  (HRSA)
• Developed tool My Family Health Portrait
• Download free at http//www.hhs.gov/familyhistory
• Focuses on chronic diseases

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US Surgeon Generals Family History Initiative

• Increase awareness among the public and health
  professionals of the value of family history for
  disease prevention and health promotion
• Provide
• Tools to gather information, assess risk, and
  guide prevention strategies
• Educational materials to facilitate communication
  about familial risk between patients and
  providers
• Increase genomics and health literacy
• Prepare the public and health professionals for
  the coming era of genomic medicine

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Criteria for Diseases Included in My Family
Health Portrait

• Substantial public health burden
• Clear case definition
• High awareness of disease status among relatives
• Accurate reporting by family members
• Family history is an established risk factor
• Effective interventions for primary and secondary
  prevention

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My Family Health Portrait

• Diseases included
• Stroke
• Type 2 diabetes
• Cancer
• Breast
• Colorectal
• Ovarian
• Information may be taken electronically or using
  paper and pencil instruments

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My Family Health Portrait

• Information collected
• Age, gender, race / ethnicity
• Number of relatives in each category (mother,
  father, children, etc.)
• Specific for 1st and 2nd degree relatives
• History of 6 diseases, age at diagnosis
• Questions about results of screening tests,
  frequency / reasons for clinician visits
• Risk factors (e.g., BMI, smoking, diet, exercise,
  etc.)

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http//www.hhs.gov/familyhistory/
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Family Healthware

• Family risk level is based on
• Number of affected family members, degree of
  relatedness, number of generations affected
• Mendelian modes of inheritance
• Risk levels
• Strong
• Affected 1st degree relative with early-onset
  disease
• Multiple affected relatives
• Hereditary syndrome suspected
• Moderate
• Affected 1st degree relative with late-onset
  disease
• Two affected 2nd degree relatives
• Average
• No 1st degree or one 2nd degree relative affected

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Familial Risk Classification
Standard Public Health Prevention Recommendations
Average
Family Health Portrait
Personalized Prevention Recommendations
Moderate
Personalized Prevention Recommendations
and Referral
Strong
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Family Healthware

• Prevention messages are based
• Familial risk level
• Answers to question about screening tests
• Health behaviors
• Age
• Gender
• Evidence-based prevention approaches

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Prevention Strategies for High Risk Families

• Targeted lifestyle changes such as diet, exercise
  and stopping smoking
• Screening at earlier ages, more frequently and
  with more intensive methods than might be used of
  average risk individuals
• Use of chemoprevention approaches
• Aspirin
• Referral to a generalist or specialist

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Prevention Strategies for High Risk Families

• Will identification of high risk families lead to
  behavior change?
• Positive and negative studies
• Consider the tool used for data collection
• Interactive vs. web-based tools
• Complete at home, with input from family members
• In clinicians office
• Personal digital assistants (PDAs)
• With evidence-based guidelines, monitoring and
  feedback options

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Evaluation of Family History Tools

• Before family history is accepted as a screening
  tool, must evaluate
• Accuracy and reliability
• Effectiveness of risk stratification on early
  detection and prevention
• 4 components of evaluation
• Analytical validity
• Clinical validity
• Clinical utility
• Ethical, legal and social issues
• Same issues would need to be addressed before
  genetic testing could be used as a screening tool

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Evaluation Framework