Summary of GeneTests Database Analysis

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Family History for Public Health and Preventive
Medicine Developing a Research Agenda

• Paula Yoon, ScD, MPH

Office of Genomics Disease PreventionCDC
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Why this workshop --
Could disease information about a persons close
relatives be used to predict their own risk for
specific diseases?
Would individuals who may be at above average
risk benefit from targeted interventions beyond
what is recommended for the population at large ?
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Purpose of the workshop --
Discuss the potential of family history for
disease prevention and determine what information
is needed in order to assess the validity and
utility of this approach.
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Workshop goals --

• Identify diseases and selection criteria
• Describe specifications for a FH tool
• Identify knowledge gaps in AV, CV, CU
• Describe ethical, legal and social implications
• Describe studies needed to fill knowledge gap
• Identify potential sources of existing data
• Describe new studies that may be needed

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What is family history?

• reflects the consequences of genetic
• susceptibilities, shared environment, and
• common behaviors
• ranges from knowing whether a parent or
• sibling had a specific disease to a very
• detailed pedigree analysis

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Family history for public health and preventive
medicine

• simple, easily applied, inexpensive
• can identify people at high and moderate risk
• can be used in combination with other risk
• factors
• useful for targeting interventions
• positively influences healthy behaviors

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Family history for public health and preventive
medicine

• population-based uses of FH
• e.g., Behavioral Risk Factor Surveillance System
  
• stratify risk factors by FH
• target interventions
• evaluate trends over time

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Prevalence and relative risk estimates due to
family history for chronic diseases
CVD 58 mill 2.0 5.4 Breast cancer 3 mill
wom 2.1 3.9 Colorectal incid 130,000 1.7
4.9 Prostate incid 200,000 3.2
11.0 Melanoma 200,000 2.7 4.3 Type II
diabetes 13 mill 2.4 4.0 Osteoporosis 8 mill
wom 2.0 2.4 2 mill men Asthma 17 mill 3.0
7.0
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Risk estimates for colorectal cancer for 3
family history risk groups
Average Moderate High (no
FH) (one 1 relat) (gtone 1
relat) FH preval 9/10 1/10 1/50 ---
1/8,000 Absolute 0.04 0.06 0.20 ---
1 Relative ref 1.7 4.9 ---
30 Attributable 0.07 0.07 --- 0.004
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Evaluation framework
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Analytic validity --
How accurately and reliably does the FH tool
identify disease among a persons relatives?
gold standard -
A B - C D
FH tool
analytic sensitivity A / (AC) analytic
specificity D / (BD)
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Clinical validity --
How accurate and reliable is FH for stratifying
disease risk and predicting future disease?
Future disease -
A B - C D
FH
clin sensitivity A / (AC)
clin specificity D / (BD) PPV A /
(AB) NPV D / (CD)
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Clinical utility --
What are the benefits and risks accruing from
both negative and positive family history?

• will targeted interventions based on FH
• prevent disease?
• is FH useful for changing behavior?
• is the approach cost-effective?
• are there risks associated with collecting
  and using FH?

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Ethical, legal and social implications --

• stigma associated with above average risk
• psychological impact of risk label
• discrimination or adverse effects on personal
• and family life
• informed consent requirements
• safeguards to protect privacy and confidentiality

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Evaluation framework
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Potential of family history
Jim Fixx 1932 - 1984