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 FH is risk factor for many common diseases current strategies not working (diet, exercise, smoking) Jim Fixx

Risk factors for common disease Obesity

Risk factors for common disease Exercise - only 25% of adults engage in recommended physical activity levels

Risk factors for common disease Smoking

Public health impact of common disease Diabetes – 6 th 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 – 3 rd leading cause of death; 600,000 new or recurrent strokes per year Breast cancer – most common cancer diagnoses in women and 2 nd cancer-related deaths; 203,500 new cases in 2002 Prostate cancer - most common cancer diagnosis in men and 2 nd cancer-related deaths; 189,000 new cases in 2002 Colon cancer – 3 rd most common cancer diagnosis and cancer- related 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

Could disease information about a person’s close relatives be used to predict their own risk for specific diseases? Basic issues – validity and utility 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

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): panel of experts – May articles in Am J Prev Med - Feb 2003 family history work group development of research agenda and criteria for tools Phase 1 - Assessment

8 criteria for inclusion of diseases 1.Public health burden 2.Well defined case definition 3.High awareness of disease status among relatives 4.Accurately reported by relatives 5.Family history is a risk factor 6.Population prevalence of family history as a risk factor 7.Effective interventions for primary and secondary prevention 8.Different recommendations for familial risk groups

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 Phase 2 – Tool development

Family History Tool Average Moderate High Standard prevention recommendations Personalized prevention recommendations Referral for genetic evaluation and personalized prevention recommendations ClassificationIntervention Assessment Using family history for disease prevention

What makes a family history tool useful for public health and preventive medicine ? 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 Family History Tool

18 diseases (year that defines early onset) - 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) 1 st draft Family History Tool

Algorithms for classifying risk Family History Tool Scheuner M et al. Am J Med Genet 1997;71:

Resource manual for primary care Family History Tool Binder with chapter for each disease 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 CVD1 1 st -degree relative moderate60% diagn >60 yrs Colorectal2 1 st -degree relatives high 50% Cancer1 diag <50 yrs Melanomanoneaverage<1% ConditionFamily HistoryRisk GroupLifetime Risk

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

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 Phase 3 – Pilot testing and Evaluation

ACCE Evaluation framework

A nalytic validity – sensitivity, specificity How well does the tool measure disease status among a person’s relatives? C linical validity – predictive value How accurate is FH data for stratifying disease risk and predicting future disease? ACCE Evaluation

C linical utility – interventions, cost What are the benefits and risks from both negative and positive family histories? Are there effective interventions available for primary and secondary prevention? Will targeted interventions based on FH have an impact on disease prevention? Is the approach cost-effective? ACCE Evaluation

E thical, Legal, and Social Implications 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? ACCE 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

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 – a “genomic tool”

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