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

• Paula Yoon, ScD, MPH

Office of Genomics & Disease PreventionCDC

Could disease information about a person’s close relatives be used to predict their own risk for specific diseases?

Why this workshop --

Would individuals who may be at above average risk benefit from targeted interventions beyond what is recommended for the population at large ?

Purpose of theworkshop --

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.

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

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

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

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

Prevalence and relative risk estimates due

to family history for chronic diseases CVD 58 mill 2.0 – 5.4Breast cancer 3 mill wom 2.1 – 3.9Colorectal incid = 130,000 1.7 – 4.9Prostate incid = 200,000 3.2 – 11.0Melanoma 200,000 2.7 – 4.3Type II diabetes 13 mill 2.4 – 4.0Osteoporosis 8 mill wom 2.0 – 2.4

2 mill menAsthma 17 mill 3.0 – 7.0

Risk estimates for colorectal cancer for 3 family history risk groups

Average Moderate High

(no FH) (one 1° relat) (>one 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

Evaluation framework

Effective Intervention(Benefit)

NaturalHistory

EconomicEvaluation

QualityAssurance

Education Facilities

PilotTrials

Monitoring&

Evaluation

Ethical, Legal, &Social Implications

(safeguards& impediments)HealthRisks

ClinicalSpecificity

ClinicalSensitivity Prevalence

PPVNPV

Penetrance

Assay Robustness

QualityControl

AnalyticSpecificity

AnalyticSensitivity

Disorder&

Setting

Analytic validity --

How accurately and reliably does the FH tool identify disease among a person’s relatives?

FH tool

“gold standard” + -

+ A B - C Danalytic sensitivity = A / (A+C)

analytic specificity = D / (B+D)

Clinical validity --

How accurate and reliable is FH for stratifying disease risk and predicting future disease?

FH

Future disease + -

+ A B - C D clin sensitivity = A / (A+C)

clin specificity = D / (B+D)PPV = A / (A+B)NPV = D / (C+D)

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?

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

Evaluation framework

Effective Intervention(Benefit)

NaturalHistory

EconomicEvaluation

QualityAssurance

Education Facilities

PilotTrials

Monitoring&

Evaluation

Ethical, Legal, &Social Implications

(safeguards& impediments)HealthRisks

ClinicalSpecificity

ClinicalSensitivity Prevalence

PPVNPV

Penetrance

Assay Robustness

QualityControl

AnalyticSpecificity

AnalyticSensitivity

Disorder&

Setting

Potential of family history

Jim Fixx 1932 - 1984