Moving the Needle on Action Around Evidence-Based Screening for Hereditary Conditions: Preparing State Chronic Disease Directors to Advance Precision Public Health

The completion of the Human Genome Project spurred the development of genomic applications to identify persons at increased risk for common chronic conditions, such as cancer and cardiovascular disease. These developments elevated expectations that genomics will usher in an era of “personalized medicine,” in which physicians and other health care practitioners can more precisely target preventive interventions and therapies based on the genomic profiles of individual patients. A parallel concept, precision public health, also emerged and is defined as providing the right intervention to the right population at the right time.^1,2 This targeted population approach has the potential to reduce morbidity and mortality from these chronic conditions. Moreover, public health agencies play an important role in monitoring for the emergence of health inequalities and are important gatekeepers in broadening access to new technologies and reducing health disparities for the most vulnerable segments of our population.²

In recognition of the role that public health genomics can play in population-level health promotion, the US Department of Health and Human Services added genomics as a topic area to the Healthy People 2020 objectives in 2010, by recommending that women with a strong family history of breast and/or ovarian cancer be referred for genetic counseling and increasing the percentage of persons with newly diagnosed colorectal cancer to receive genetic testing for Lynch syndrome (and further cascade screening of family members).^3,4 Also in 2010, the Centers for Disease Control and Prevention’s (CDC’s) Office of Public Health Genomics created a framework for identifying emerging genomic applications with the highest potential for improving population health.⁵ This framework comprises 3 tiers:

1. Tier 1: synthesized, evidence-based guidelines/recommendations that support broad implementation because they have the potential to improve population health through early detection and intervention (eg, newborn screening)

2. Tier 2: insufficient evidence for implementation that requires informed decision making for selective use (eg, single gene disorders)

3. Tier 3: evidence that discourages use or evidence that is nonexistent (eg, routine population breast and ovarian cancer counseling and testing)^6,7

Currently, only 3 major adult-onset disease applications have accumulated sufficient evidence to warrant placement in the Tier 1 category: hereditary breast and ovarian cancer, Lynch syndrome, and familial hypercholesterolemia.^6,8 Early detection and possible referral for intensive or early screening and systematic family tracing (ie, cascade screening) to identify high-risk persons are important components of each of these applications.⁹ Although limited evidence suggests that early screening and referral for these genomic applications reduce morbidity and mortality, expert panels reasoned that connecting people to screening and treatment could plausibly improve individual health outcomes and thereby also promote overall population health.⁸ Moreover, because cancer and heart disease are the 2 leading causes of death in the United States, costing an estimated $75 billion and $320 billion, respectively, per year, and hereditary breast and ovarian cancer, Lynch syndrome, and familial hypercholesterolemia collectively affect more than 2 million persons, concerted action on the Tier 1 screening recommendations could reduce health care expenditures (Table).^8–19

Table.

Public health prevalence and impacts of Tier 1 conditions, United States, 2018

Impact	Condition
	Breast Cancer	Ovarian Cancer	Colon Cancer	Cardiovascular Disease
Public health Importance	Most common cancer among women10; second most common cause of cancer death10	5% of cancer deaths among women10	Third most common cancer among men and women10; third most common cause of death among men and women10	Leading cause of death among men and women11
Estimated total new adult cases in 2018, no.	266 120 women,10 2550 men10	22 24010	97 22010	73.5 million in population (31.4%)11
Prevalence of mutation in new cases, %	2-711	10-1511	512	NA
Potential identification per year through Tier 1 recommendations, no.b	5373-18 807	2224-3336	4861	NA
Risk of disease with mutation, %	38-8713,a	17-6313,a	8014	Men, 50; women, 3015
Estimated prevalence of mutation in US population, ratio	1:400-1:50013,a	1:400-1:50013,a	1:37016	1:250-1:50015,c
Estimated US population carrying mutation, no.d	658 000-822 50013,a	658 000-822 50013,a	889 18914	658 000-1 316 00017,c
Yearly deaths, no.	40 920 women10	14 07010	50 63010	836 54618

Abbreviation: NA, not available.

^aRates were significantly higher among the Ashkenazi Jewish population.

^bBased on calculation of total new cases and prevalence of new mutation. Does not include family members potentially identified through cascade screening.

^cEstimated higher rates in European white populations.

^dBased on estimated 2018 US population of 329 million.¹⁹

State health departments could play an important role in advancing precision public health by promoting the appropriate use of genomics to benefit population health, but little is known about their capacity to do so. For decades, genetics activities at state health departments have focused on newborn screening, birth defects surveillance, and supportive services for children with genetic diseases (eg, sickle cell disease). For precision public health to become a reality, it will be necessary to assess the capacity of state health agencies to integrate genomics into their chronic disease programming, especially for the Tier 1 conditions that have already shown potential to improve population health.^20,21 State health agencies are often underfunded, however, which compromises traditional programming for chronic disease prevention, let alone adoption of novel technologies and screening recommendations.^22,23 Determining how to support states in incorporating genomics into chronic disease prevention in a climate of funding constraints should be a priority.

Role of Federal Agencies and State Health Departments

Since 2003, CDC has provided limited funding to state health agencies to pilot methods of integrating Tier 1 applications into state chronic disease programming; however, this support has been received by only 7 states (Colorado, Connecticut, Georgia, Michigan, Minnesota, Oregon, and Utah).^20,24 Nevertheless, these pilot programs suggested that a precision public health approach using genomics could improve health. Initial projects commonly used several distinct strategies: educating the public about the importance of knowing one’s family history, incorporating evidence-based recommendations for genomics screening into chronic disease programs, and disseminating educational resources to health care providers, policy makers, and the public.²⁴ To date, 32 states have integrated at least 1 genomics-related goal into their state cancer control plans, whereas the 7 CDC-funded states have undertaken more ambitious efforts, for example, adding questions to their state’s Behavioral Risk Factor Surveillance System (BRFSS) to determine what residents of their states know about genomics, analyzing state cancer registry data to estimate the public health burden of hereditary cancer on residents of their state, evaluating the use of genetic counseling and testing services, and identifying ways to improve access to these services among persons at high risk of chronic diseases.^20,24-29 Furthermore, as the unbiased conveners of public health programming, state health agencies could implement genomics while monitoring for the emergence of health inequities (eg, differential access to genetic services among medically underserved groups) and intervening where feasible.²⁹ For example, CDC-funded pilot programs tailored family health history education to be culturally sensitive to the needs and concerns of racial/ethnic minority groups and residents of rural communities.³⁰ State health agencies also educated health insurers about evidence-based recommendations for Tier 1 screening, helping them broaden insurance coverage for screening and minimize cost concerns as a barrier to accessing care.³¹

Chronic Disease Directors as Champions of Precision Public Health

In state health agencies, chronic disease directors (CDDs) who lead prevention efforts are potentially positioned to champion genomics implementation and move toward precision public health, especially because all 3 Tier 1 recommendations relate to common chronic diseases that are already in their purview.³² Leadership by CDDs could be helpful not only in advancing such integration but also in assessing program effectiveness, educating health care providers and the public, and facilitating collaborations with stakeholders. Although CDDs could play an instrumental role in state chronic disease genomics programming, little is known about their current knowledge, preparedness, or interest in doing so. Understandably, CDDs may need some assistance in determining which genomic applications are ready for implementation and which evidence-based recommendations apply. Moreover, information about implementation strategies that have been piloted successfully elsewhere and suggestions for tailoring these strategies to their state’s needs might also prove helpful.³³

We conducted an online survey of all state and territorial CDDs in the United States (n = 58) from February 11 through March 31, 2016, to assess any current state genomics activities related to Tier 1 conditions, CDDs’ knowledge of Tier 1 conditions, and CDDs’ interest in integrating genomics into chronic disease programming. The number of respondents (n = 16), although within the range achieved in previous surveys by this method,³⁴ did not allow us to draw conclusions about knowledge and interest in genomics among the wider population of CDDs. However, it did provide insight into what a subset of CDDs who hold leadership positions in state health agencies currently know about genomics and how ready they are to take action on Tier 1 conditions.

Not surprisingly, we found that few respondent states had embraced genomics activities into their chronic disease prevention programs (hereditary breast cancer education [n = 5], hereditary ovarian and colorectal cancer education [n = 4], incorporating genomics into state cancer control plan [n = 4], incorporating genomics into cancer screening section of BRFSS and using state cancer registry to identify persons affected by hereditary cancer syndromes [n = 3]). Fortunately, the level of interest in incorporating specific genomics activities into chronic disease prevention was high (range: 7-12). We also found that knowledge of Tier 1 chronic disease conditions was limited among the CDDs who responded. On a scale from 1-5, where 1 was poor and 5 was very good, median (standard deviation [SD]) knowledge of hereditary breast and ovarian cancer was 3.1 (1.5), of familial hypercholesterolemia was 2.5 (1.3), and of Lynch syndrome was 2.1 (1.3). Moreover, only a small number of CDDs were contacting or collaborating with professionals outside the state health department about genomics in the past quarter/year (academic institutions [n = 5 quarter; n = 1 year], primary care providers [n = 5 quarter; n = 0 year], genetic counselors [n = 4 quarter; n = 1 year], other clinicians [n = 4 quarter; n = 1 year], advocacy groups [n = 4 quarter; n = 1 year], hospitals/health care systems/third-party payers [n = 3 quarter; n = 1 year], local and county health departments [n = 1 quarter; n = 1 year]).

We were, however, encouraged to learn that CDDs believed that taking action on the Tier 1 applications could improve the health of their state’s residents (n = 12). Eleven CDDs considered genomics integration into chronic disease programming to be beneficial to individuals and families in their state, and 8 CDDs agreed that genetics should be an important component of public health initiatives. On the other hand, only 7 CDDs thought that their staff members understood how genetics relates to chronic disease, 5 believed that their citizens recognized how family history or genetics can influence chronic disease risk, and only 2 were confident that legal protections were adequate in their state (beyond legal protections provided by the federal Genetic Information Nondiscrimination Act of 200 8³⁵) to protect against genetic discrimination.

Recommendations

Based on the findings of our survey, we suggest several steps that state and territorial CDDs could take to embrace precision public health by making progress on Tier 1 genomics implementation. We understand that financial constraints are pervasive and the population health benefits of many genomic discoveries are still unclear. As such, our suggestions are based on low-cost efforts for the conditions that have already met Tier 1 criteria. CDC’s Office of Public Health Genomics provides several resources, templates, and samples in its online toolkit³⁶ and its state clickable map,²⁸ which allow CDDs to identify local, state, and/or regional partners.

We recommend that CDDs

1. Integrate genomics into chronic disease plans (eg, incorporate hereditary breast and ovarian cancer and Lynch syndrome screening into the state cancer plan and familial hypercholesterolemia into the state cardiac disease plan).

2. Develop educational materials for health professionals, policy makers, and the public (eg, educate policy makers about genetic testing threats to privacy, ensuring residents in the state are adequately protected; educate the public about how family history and genetics can influence the risk of chronic disease)

3. Add genomics questions to the BRFSS (eg, assess the public’s knowledge about genetic screening and concerns they may have about genetic discrimination and monitor for racial/ethnic disparities in accessing cancer genomic screening services). Sample questions can be found on the University of Washington Center for Genomics and Public Health website.³⁷

4. Use state cancer registry data to help hospitals and providers identify at-risk individuals (eg, provide facility-specific data and, when requested, report a confidential and consolidated list of residents with certain types of cancer, such as breast, ovarian, or colon cancer; provide educational materials to hospitals and providers to encourage referral of affected patients and their family members to genetics service providers).

5. Forge collaborations with external partners on genomics, especially genetic counselors, academic centers, and primary care providers, to increase knowledge and awareness of genomic topics, implementation considerations, and policy implications.

6. Develop and advocate for ways to lower barriers to access for their state’s population (eg, educate providers, the public, and insurers about the appropriateness of genomics applications).

7. Investigate novel avenues to reduce testing and treatment costs (eg, identify research studies, work to change Medicare/Medicaid reimbursement policies, collaborate with large testing facilities or health systems to offer reduced-price or free testing in exchange for HIPAA [Health Insurance Portability and Accountability Act of 1996]–protected patient data, facilitate genetic counseling referrals).

Conclusion

Integrating genomics into chronic disease programming is a practical, viable step to advance precision public health. CDDs are in a potentially powerful position to foster the leadership, knowledge, and collaborations that could bring the benefits of genomics to wider populations and ensure equitable access. We identified several strategies that can move Tier 1 chronic disease genomics implementation forward, even with modest resources. CDDs can tailor or adapt existing resources and form collaborations and partnerships to facilitate implementation of Tier 1 chronic disease applications. Moving the needle on precision public health by implementing these Tier 1 applications has the potential to reduce the public health burden and associated costs of chronic conditions and is a worthwhile public health prevention objective.