Integrating Genomics into Clinical Practice Jan Dorman, PhD University of Pittsburgh School of Nursing

Applications of Genomics to Clinical Practice Molecular diagnosis –$1000 for human genome sequence Prediction of a healthy person’s risk of disease –Including cancer, cardiovascular disease, diabetes, etc. Evaluation of responses to drugs and environmental agents –Pharmacogenomics

Where do clinicians begin? Begin with assessment of family history “Even when an individual’s genome can be displayed on a personal microchip, interpreting that information will depend in large part, on the biological and environmental contexts in which the genome is expressed, and the family milieu is as good a guide as any.” Pyeritz RE. JAMA 278:

Family Health History Is an important risk factor for chronic diseases that reflects –Inherited genetic susceptibility –Shared environment risk factors (diet) –Cultural factors (religious practices) –Common behaviors (smoking, physical activity) Prior to offering any genetic susceptibility testing, a clinician needs to assess the family history of disease –Who should be tested? –What genes should be tested?

Family History of Diabetes T2D is an independent risk factor for the disease 88-95% have affected 1 st degree relatives –70-77% have affected 2 nd degree relative Individuals with a positive family history are about 2-6 times more likely to develop T2D than those with a negative family history –Risk ~40% if 1 T2D parent; ~80% if 2 T2D parents

Family History of Diabetes FH identifies a group of high risk individuals –Using a simple and inexpensive approach –Who may benefit from early detection –To develop personal and family-based risk factor modification strategies –In the future, may benefit from genetic testing Has been difficult to find genes for T2D –Late age at onset –Polygenic inheritance Multiple genes with small effects –Multifactorial inheritance

Collecting Family History Information in Clinical Practice Barriers –Underestimation (by clinicians and patients) of value of family history information –Limited knowledge and training in human genetics National Coalition for Health Professional Education in Genetics (NCHPEG) endorsed core competencies for all health-care professionals in 2000

NCHPEG Core Competencies Represents minimum knowledge, skills and attitudes necessary for health professionals in all disciplines to provide patient care that involves awareness of genetic issues and concerns –Medicine- Dentistry –Nursing- Psychology –Public Health- Social work

NCHPEG Core Competencies Appreciate limitations of his or her genetic expertise Understand the social and psychological implications of genetics Know how and when to make a referral to a genetic professional

Some NCHPEG Recommendations Knowledge –Importance of family history (minimum of 3 generations) in assessing predisposition to disease –The range of genetic approaches to treatment of disease –Resources available to assist clients seeking genetic information –The indications for genetic testing and / or gene-based interventions

Some NCHPEG Recommendations Skills –Gather genetic FH information, including multiple generation pedigrees –Identify families who would benefit from genetic services Educate individuals regarding these services, and their risks and benefits Attitudes –Appreciate the sensitivity of genetic information and the need for privacy and confidentiality –Demonstrate willingness to update genetics knowledge at frequent intervals

Other barriers –Lack of time –Lack of reimbursement for collecting the information –Concerns about insurance / employment discrimination –Lack of convenient tools / software for data collection Collecting Family History Information in Clinical Practice

Popular Literature Family History Tools in the

US Surgeon General’s Family History Initiative First National Family History Day, Thanksgiving, 11/25/2004 US Partners –Office of the Surgeon General –National Human Genome Research Institute (NHGRI) –Centers for Disease Control and Prevention (CDC) –Agency for Healthcare Research and Quality (AHRQ) –Health Resources and Services Administration (HRSA) Developed tool “My Family Health Portrait” –Download free at –Focuses on chronic diseases

US Surgeon General’s Family History Initiative Increase awareness among the public and health professionals of the value of family history for disease prevention and health promotion Provide –Tools to gather information, assess risk, and guide prevention strategies –Educational materials to facilitate communication about familial risk between patients and providers Increase genomics and health literacy Prepare the public and health professionals for the coming era of genomic medicine

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Criteria for Diseases Included in “My Family Health Portrait” Substantial public health burden Clear case definition High awareness of disease status among relatives –Accurate reporting by family members Family history is an established risk factor Effective interventions for primary and secondary prevention

“My Family Health Portrait” Diseases included –Stroke –Type 2 diabetes –Cancer Breast Colorectal Ovarian Information may be taken electronically or using paper and pencil instruments

“My Family Health Portrait” Information collected –Age, gender, race / ethnicity –Number of relatives in each category (mother, father, children, etc.) Specific for 1 st and 2 nd degree relatives –History of 6 diseases, age at diagnosis –Questions about results of screening tests, frequency / reasons for clinician visits –Risk factors (e.g., BMI, smoking, diet, exercise, etc.)

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“Family Healthware” Family risk level is based on –Number of affected family members, degree of relatedness, number of generations affected –Mendelian modes of inheritance Risk levels –Strong Affected 1 st degree relative with early-onset disease Multiple affected relatives Hereditary syndrome suspected –Moderate Affected 1 st degree relative with late-onset disease Two affected 2 nd degree relatives –Average No 1 st degree or one 2 nd degree relative affected

Familial Risk Classification Family Health Portrait Average Personalized Prevention Recommendations and Referral Personalized Prevention Recommendations Standard Public Health Prevention Recommendations Moderate Strong

“Family Healthware” Prevention messages are based –Familial risk level –Answers to question about screening tests –Health behaviors –Age –Gender –Evidence-based prevention approaches

Prevention Strategies for High Risk Families Targeted lifestyle changes such as diet, exercise and stopping smoking Screening at earlier ages, more frequently and with more intensive methods than might be used of average risk individuals Use of chemoprevention approaches –Aspirin Referral to a generalist or specialist

Prevention Strategies for High Risk Families Will identification of high risk families lead to behavior change? –Positive and negative studies Consider the tool used for data collection –Interactive vs. web-based tools Complete at home, with input from family members In clinician’s office –Personal digital assistants (PDAs) With evidence-based guidelines, monitoring and feedback options

Evaluation of Family History Tools Before family history is accepted as a screening tool, must evaluate –Accuracy and reliability –Effectiveness of risk stratification on early detection and prevention 4 components of evaluation –Analytical validity –Clinical validity –Clinical utility –Ethical, legal and social issues Same issues would need to be addressed before genetic testing could be used as a screening tool

Evaluation Framework