Summary of GeneTests Database Analysis

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Family History for Public Health
and Preventive Medicine
Paula W. Yoon, ScD, MPH
Office of Genomics & Disease
Prevention, CDC
'This is happening every day'
(CNNSI Online-June 24, 2002)
• “Kile's father's death from cardiovascular disease in
his 40s should have been a red flag signaling that the
pitcher had an increased risk of the same fate”
• “Patients with a strong family history should get
rigorous routine checkups including cholesterol
screening, exercise stress tests or heart imaging
tests”
Why focus on family history?
• news stories about sudden cardiac death
• FH is underutilized in preventive medicine
• geneticists use of pedigrees
Jim Fixx 1932 - 1984
• FH is risk factor for many common diseases
• current strategies not working (diet, exercise, smoking)
Risk factors for
common disease
Obesity
Risk factors for
common disease
- only 25% of adults engage in
recommended physical activity
levels
Exercise
Risk factors for
common disease
Smoking
Public health impact of common disease
Diabetes – 6th leading cause of death; prevalence 7.3% in 2000
Coronary Heart Disease – leading cause of death & disability;
lifetime risk after age 40 is 49% males and 32% females
Stroke – 3rd leading cause of death; 600,000 new or recurrent
strokes per year
Breast cancer – most common cancer diagnoses in women and 2nd
cancer-related deaths; 203,500 new cases in 2002
Prostate cancer - most common cancer diagnosis in men and 2nd
cancer-related deaths; 189,000 new cases in 2002
Colon cancer – 3rd most common cancer diagnosis and cancerrelated death; 148,300 new cases in 2002
Family history is an independent risk
factor for most chronic diseases of public
health significance
What is family history?
reflects the consequences of genetic
susceptibilities, shared environment, and
common behaviors
Family history is a risk factor for
common diseases – AJPM Feb 2003
• Population-based studies RR estimates –
CHD 2-5
type II diabetes 2-6
asthma 2-4
breast cancer 2-6
colorectal cancer 2-5
• FHx explains a significant fraction of prevalent CHD –
14% Utah families had 72% early CHD and 48% all CHD
• 5-20% of people report a FHx of colorectal cancer
Basic issues – validity and utility
Could disease information about
a person’s 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 ?
Family History Public
Health Initiative
Evaluate the use of family history for assessing risk of
common diseases and influencing early detection and
prevention strategies
• Phase 1 – Assessment of existing strategies and
development of criteria for FH tool
• Phase 2 – Tool development
• Phase 3 – Pilot testing and evaluation
• *Phase 4 - public health campaign and provider
education programs
Phase 1 - Assessment
• literature review - evidence and identify data gaps
• Can family history be used as a tool for public health and
preventive medicine? Genet in Med 2002; 4(4):304-310
• panel of experts – May 2002
• 10 articles in Am J Prev Med - Feb 2003
• family history work group
• development of research agenda and criteria for tools
8 criteria for inclusion of diseases
1.
2.
3.
4.
5.
6.
7.
8.
Public health burden
Well defined case definition
High awareness of disease status among relatives
Accurately reported by relatives
Family history is a risk factor
Population prevalence of family history as a risk factor
Effective interventions for primary and secondary prevention
Different recommendations for familial risk groups
Phase 2 – Tool development
• review of existing FH tools
• ongoing analysis of existing data sets – e.g, ARIC
• selection of diseases based on criteria
• development of FH tool and algorithms for risk
categorization
• development of resource manual for primary care
Using family history for disease prevention
Assessment
Classification
Average
Family
History
Tool
Intervention
Standard prevention
recommendations
Moderate
Personalized prevention
recommendations
High
Referral for genetic
evaluation and personalized
prevention recommendations
What makes a family history tool
useful for public health and
preventive medicine ?
Family
History
Tool
•
simple, easily applied, adaptable
•
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
18 diseases (year that defines early onset)
Family
History
Tool
1st draft
-
coronary heart disease (60)
sudden unexpected death (40)
stroke/TIA (mini stroke) (60)
hypertension (40)
diabetes (20)
blood clots in lungs or legs (40)
emphysema/lung disease (50)
kidney disease (50)
breast cancer (50)
ovarian cancer (50)
prostate cancer (50)
colon/colorectal cancer (50)
endometrial cancer (50)
thyroid cancer (50)
kidney cancer (50)
Algorithms for
classifying risk
Family
History
Tool
Scheuner M et al.
Am J Med Genet
1997;71:315-324.
Binder with chapter for each disease
Resource
manual for
primary care
Family
History
Tool
• recommended interventions for each level of
risk
e.g., colorectal cancer
Average – screening at age 50
Moderate – screening at age 40?
High – referral for genetic consult
• explanation of potential Mendelian conditions
underlying high risk
e.g., HNPCC, APC
• additional resources - web sites, brochures
Results of FHx screening for
hypothetical, healthy 23-yr-old male
Condition
Family History
Risk Group
Lifetime
Risk
CVD
1 1st-degree relative
diagn >60 yrs
moderate
60%
Colorectal
Cancer
2 1st-degree relatives
1 diag <50 yrs
high
50%
Melanoma
none
average
<1%
Settings and informatics
Electronic tool with applications
• Personal computers
• Internet
• Hand-held devices
Potential settings
• primary care providers
• public health clinics
• drug stores, schools
• home
Phase 3 – Pilot testing
and Evaluation
• develop pilot studies to fine tune the tool
• create funding opportunities
• evaluate the tool, algorithms and resource manual
in different settings and populations
• evaluation framework - ACCE
ACCE Evaluation framework
Effective
Intervention
(Benefit)
Natural
History
Quality
Assurance
Clinical
Sensitivity Prevalence
Clinical
Specificity
Ethical, Legal, &
Social Implications
(safeguards& impediments)
Pilot
Trials
PPV
NPV
Disorder
&
Setting
Penetrance
Analytic
Assay
Sensitivity
Robustness
Analytic Quality
Specificity Control
Monitoring
&
Evaluation
Education
Facilities
Health
Risks
Economic
Evaluation
Effective
Intervention
(Benefit)
ACCE Evaluation
Natural
History
Quality
Assurance
Clinical
Sensitivity Prevalence
Clinical
Specificity
Ethical, Legal, &
Social Implications
(safeguards& impediments)
Pilot
Trials
PPV
NPV
Disorder
&
Setting
Penetrance
Analytic
Assay
Sensitivity
Robustness
Analytic Quality
Specificity Control
Monitoring
&
Evaluation
Education
Analytic validity – sensitivity, specificity
How well does the tool measure disease status
among a person’s relatives?
Clinical validity – predictive value
How accurate is FH data for stratifying disease
risk and predicting future disease?
Facilities
Health
Risks
Economic
Evaluation
ACCE Evaluation
Effective
Intervention
(Benefit)
Natural
History
Clinical
Specificity
Ethical, Legal, &
Social Implications
(safeguards& impediments)
Clinical utility – interventions, cost
Disorder
&
Setting
Penetrance
Monitoring
&
Evaluation
Education
• Are there effective interventions available for
primary and secondary prevention?
• Is the approach cost-effective?
Pilot
Trials
PPV
NPV
Analytic
Assay
Sensitivity
Robustness
Analytic Quality
Specificity Control
What are the benefits and risks from both
negative and positive family histories?
• Will targeted interventions based on FH
have an impact on disease prevention?
Quality
Assurance
Clinical
Sensitivity Prevalence
Facilities
Health
Risks
Economic
Evaluation
ACCE Evaluation
Effective
Intervention
(Benefit)
Natural
History
Quality
Assurance
Clinical
Sensitivity Prevalence
Clinical
Specificity
Ethical, Legal, &
Social Implications
(safeguards& impediments)
Ethical, Legal, and Social Implications
Pilot
Trials
PPV
NPV
Disorder
&
Setting
Penetrance
Analytic
Assay
Sensitivity
Robustness
Analytic Quality
Specificity Control
Monitoring
&
Evaluation
Education
Are there issues affecting data collection and
interpretation that might negatively impact
individuals, families, and society ?
• Are there legal issues re informed consent,
ownership of the data, or obligation to disclose?
• What is known about stigmatization,
discrimination, privacy/confidentiality, and
personal, family and social issues associated with
family history assessment and risk labeling?
Facilities
Health
Risks
Economic
Evaluation
*Phase 4 –
Public health campaign
& provider education
• develop public health messages about the value of
knowing your family history
• demo and disseminate the tools
• work with professional organizations to implement
FH collection and use
• development and implement provider education
Why would this approach
be of interest or value to
providers?
• evidence–based guidelines e.g., United States Preventive
Services Task Force (USPSTF)
• recommended by professional orgs (e.g., AAFP, ACPM)
• incentives – improving quality of care, CMEs, standardizing a
complex process, making it faster and easier, simplify billing
• adaptable technology
Family history –
a “genomic tool”
Most common diseases result from interactions of
multiple genes with multiple environmental factors
in complex patterns that - despite progress in
sequencing the human genome – are unlikley to
be fully understood in the near future.
In the meantime, family medical history represents
a “genomic tool” that can capture the interactions
of genetic susceptibility, shared environment, and
common behaviors in relation to disease risk.
Family History Work Group
Paula Yoon, CDC
Maren Scheuner, GenRisk
Kris Peterson, CDC
Chris Friedrich, Univ MS
Ann Malarcher, CDC
Daniela Seminara, NCI
Barbara Bowman, CDC
Paul Beatty, NCHS
Ladene Larsen, Dept Hlth UT
Debra Irwin, UNC
Temitope Keku, UNC
Karen Edwards, Univ WA
Jean Jenkins, NHGRI
Teri Manolio, NHLBI
Scott Ramsey, Fred Hutchinson
Sharon Kardia, U MI
Ingrid Hall, CDC
Jean Jenkins, NHGRI
Steve Coughlin, CDC
Eugene Rich, Creighton U
Theresa Finlayson, CDC
Ted Adams, Univ UT
Saul Malozowski, NIDDK
Robin Bennett, Univ WA
Ebony Bookman, NHLBI
Anupam Tyagi
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