Family History for Public Health and Preventive Medicine

1. Family History for Public Health and Preventive Medicine Paula W. Yoon, ScD, MPH Office of Genomics & Disease Prevention, CDC

2. '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”

3. 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 1932 - 1984

4. Risk factors for common disease Obesity

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

6. Risk factors for common disease Smoking

7. 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 cancer-related death; 148,300 new cases in 2002

8. Family history is an independent risk factor for most chronic diseases of public health significance

9. What is family history? reflects the consequences of genetic susceptibilities, shared environment, and common behaviors

10. Family history is a risk factor for common diseases – AJPM Feb 2003 • Population-based studies RR estimates – CHD 2-5 type II diabetes 2-6asthma 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

11. 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 ?

12. 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

13. 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

14. 8 criteria for inclusion of diseases • 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

15. 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

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

17. 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. 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) Family History Tool 1st draft

19. Algorithms for classifying risk Family History Tool Scheuner M et al. Am J Med Genet 1997;71:315-324.

20. 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 Resource manual for primary care Family History Tool

21. Results of FHx screening for hypothetical, healthy 23-yr-old male Condition Family History Risk Group Lifetime Risk CVD 1 1st-degree relative moderate 60% diagn >60 yrs Colorectal 2 1st-degree relatives high 50% Cancer 1 diag <50 yrs Melanoma none average <1%

22. 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

23. 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

24. ACCE Evaluation framework

25. ACCE Evaluation 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?

26. ACCE Evaluation Clinical 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?

27. ACCE Evaluation Ethical, 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?

28. *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

29. 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

30. 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.

31. 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