Each week, OPHG’s Genomics & Health Impact Update includes a list of articles on genomics published by CDC scientists. These articles are selected from the latest edition of Science Clips, an online bibliographic digest that CDC shares weekly with the public health community and the public. What genomic studies are CDC public health scientists doing—and which genomes are they writing about? We went to the archives to find out.

In 2012, Science Clips listed 178 articles on genomics with one or more CDC authors. Of these, 111 (62%) concerned bacterial, viral, fungal, or parasite genomes; 61 (34%) concerned the human genome; and 6 (3%) concerned genomes of other animal species (Figure).

Most of the 61 articles on human genomics were related to epidemiology. Nearly half were epidemiologic studies; others described or applied epidemiologic methods (Table).

Table. CDC-authored articles on human genomics, 2012.

Of the 111 articles that described research on microbial genomes (bacterial, viral, fungal, or parasite), approximately half (n=58) reported their source as human surveillance or clinical samples; 3 of these articles also described samples obtained from animals or animal products. Of the 58 human-derived samples, 26 (45%) were collected through surveillance or epidemiologic surveys and 10 (17%) were from outbreaks. The remaining 53 articles described samples obtained from other (non-human) sources, of which 14 (26%) described one or more animal sources, including insects, arthropods, mollusks, birds, and mammals.

Genomes are found at all three corners of the epidemiologic triangle: human or animal hosts are engaged in genomic contests with pathogens of all kinds, played out in an environment teeming with the genomes of other people, animals, plants, and microbes.

Until recently, only the simplest genomes were available to public health scientists and even those were generally known only by their fingerprints. Now, genomic sequencing technology has brought the world in reach: whole genome sequences of pathogens, to study their biology and epidemiology; animals, plants, and environmental microbes, to study their evolution and ecology through meta-genomics and microbiome analysis; and humans, to study their susceptibility, resilience, potential to transmit infection, and response to interventions. It’s a genomic world.

It has been said that the folks at the National Human Genome Research Institute (NHGRI) never pass up the chance for well-deserved celebration – and I should know, I was one of them.  Probably at least a few readers have noticed that the Human Genome Project (HGP) has celebrated a number of milestones and anniversaries over the years – and 2013 is no exception.   April 14, 2013 marks the 10^th anniversary of the completion of the Human Genome Project, and as one might expect, NHGRI has a number of commemorative events planned.  Though most individuals outside of the genomics research community think only of the most obvious output of the HGP – the actual linear sequence of A’s, G’s, C’s and T’s that make up the human blueprint , the project comprised much more than that.  Additional components included sequencing of several important model organisms, creation of maps of the human genome that have greatly facilitated the work of discovering mutations causal of disease, and development of technologies to make genomics research cheaper, faster, and more accurate.  Reflecting on the last decade of progress in basic and biomedical research made possible by genomics, it is not too difficult to conclude that the HGP was a great public investment in science made in the second half of the 20^th century.

The April 10 issue of the Journal of the American Medical Association also celebrates the 10^th anniversary of the completion of the HGP.  The issue has a sampling of research studies that showcase the advances genomics is bringing to a diversity of areas of biomedicine, include cancer care, geriatric medicine, reproductive care, and microbiology.  Additionally, there are a series of short pieces that explore aspects of genomics that are related to the implementation of genomics in clinical and public health arenas.  The issue also contains an education-oriented article reviewing some of the currently available clinical molecular diagnostic tests in terms that a clinician not steeped in genomics can follow.

Readers of this blog will probably find several of the original research articles relevant to the field of public health genomics. For example, one of the articles identifies variants associated with long QT syndrome as the likely causal factor for at least some cases of unexplained intrauterine fetal demise.  If replicated in a larger population-based study, this could have implications for the provision of prenatal screening, and potentially provide some insights on a health problem of considerable importance at a population level. Another article showcases the growing prowess of metagenomics for investigating infectious disease outbreaks through a retrospective dissection of the microbial genomics of the 2011 German toxigenic E. coli outbreak.  Not novel?  Consider that it was achieved directly from fecal samples without an intermediate culture step to isolate the potentially causal organisms.  The development of robust, open-ended, and culture-independent molecular diagnostics platforms for infectious disease could have a profound effect on clinical as well as public health laboratory practice.

Those with an interest in health disparities will likely find the article on Alzheimer’s disease of interest, though not because it is yet another genome-wide association study (GWAS).  Rather, because it is the largest GWAS study conducted to date for Alzheimer’s in African Americans, a population that is notoriously understudied in most modern biomedical research.  The findings, like most GWAS findings, are of little immediate clinical or public health use.  However they hint at differences in the genetic architecture of Alzheimer’s that may in part account for long observed epidemiologic differences between white and African American populations.

Several of the opinion pieces in the JAMA theme issue touch on issues important to public health genomics, including the role of clinicians in guiding effective use of genomic test results, and the preparedness of health informatics infrastructure in the U.S. for genome scale data.  However, the piece that is likely to be of the most interest is an article exploring the value of genomics to the health care system in the U.S. and abroad .  This article points out a variety of important conditions that must be met before health insurers, and the broader health care system, are likely to embrace genomic advances.  As well the authors discuss the need to attend to the effects that very costly, yet potentially transformative new technologies might have on health across different population groups.

Despite the considerable interest of this JAMA theme issue,  I confess to being  somewhat dissatisfied.  Undoubtedly, many of my clinical colleagues as well as those in the public health community will feel the same way.  Absent are large prospective studies demonstrating dramatic improvements in morbidity and mortality, or substantial cost savings, arising from the ability to harness the genome to combat the top 10 causes of death in the population.  However, all of us (myself included) should remember on this 10^th anniversary after the end of the HGP, that we haven’t harnessed the genome.  In fact, we have really just begun to scratch the surface of understanding how the sequence of 6 billion base pairs leads to health and disease.  Studies of clinical effectiveness, from both clinical and public health researchers, will come.  In another few decades (yes, decades), I predict that we will be amazed at how much genomics  has contributed to improving the health of individuals and populations.  I would love very much to be there for that party.

Sequencing is No Longer a Sleeping Controversy

In the classic Disney version of the fairy tale, Sleeping Beauty is hidden in the woods to protect her from the knowledge of an evil curse… but when she later pricks her finger on a spinning wheel, she falls under a fairy’s spell…

Unlike the mythical magic of centuries old stories, modern science is changing our lives in ways that are anything but fantasy.  Advances in whole genome sequencing (WGS) promise to reveal fundamental information about our risks for various diseases.  By definition WGS includes an enormous amount of data: six billion base pairs in a human’s genome.  Unfortunately, we do not yet know what to do with the great majority of these data points, a fact that will become even more important in the next decade.  For as sequencing technology becomes less and less expensive, it could soon be more economical and practical to simply conduct WGS rather than individual tests that assess one or a few genetic variants.

Two publications have now raised awareness of the potential controversies associated with the anticipated integration of WGS into clinical and public health practice.  The most recent was the American College of Medical Genetics report ACMG Recommendations for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing.   The report argued that persons whose genomes are sequenced for any medical reason should be informed, via their healthcare providers, about variants in 57 genes that put them at risk of preventable diseases – a form of “opportunistic screening”.  The second article is a commentary in the journal Genetics in Medicine entitled: We Screen Newborns Don’t We?: Realizing the Promise of Public Health Genomics. James Evans and coauthors argue for a public health approach to assess the feasibility of active population screening for selected rare genomic variants to find millions of affected people who are at risk of preventable diseases such as cancer and heart disease – a model not too dissimilar from newborn screening.  It is not clear from these two reports whether or not the list of genes recommended for opportunistic screening in medical settings is the same as the list proposed for active population screening.

With much of the genome revealed, how can we benefit from such information while we likewise protect ourselves from its potential harms?  The publications are igniting discussion about our readiness, or lack thereof, to integrate WGS into health care and disease prevention. In addition, they point to significant ethical, legal, and social implications of releasing genetic information, incidental or otherwise, back to patients or healthy persons, when the clinical validity and utility of this information have not been established.  Indeed, ACMG acknowledges that “there are insufficient data on clinical utility to fully support [its] recommendations”.  As a test in clinical practice, our office classifies WGS as a “tier 3” application due to critical gaps in our knowledge on analytic validity, as well as clinical validity and utility.

Furthermore, interpretation of genetic variants is highly contextual and is based on age, family history, clinical presentation, and environmental factors.  For example, for BRCA testing, the US Preventive Services Task Force recommended that women with increased family history risk for hereditary breast and ovarian cancer be offered genetic counseling for testing while recommending against routine BRCA screening for women without family history risk.  Similarly, The Task Force recommended against testing for hereditary hemochromatosis in the general population. More recently, the EGAPP working group recommended against testing for Factor V Leiden for adults with idiopathic venous thromboembolism and their family members, and they found insufficient evidence for testing for genetic risk assessment for diabetes and for cardiovascular disease in the general population.

As important, there are significant ethical concerns about the return of genetic information, especially for children.   True informed consent is a must but may be difficult to achieve in practice. Meanwhile, proponents argue that people have a right to know their own biological data and make their own decisions.  Others argue that genomic data are not really information if we don’t know what they mean.  In addition to psychosocial and medical  harms, premature use of genetic information in health care could lead to a cascade of increased health care costs resulting in further testing and unproven interventions.  These issues are not new but are increasingly coming to the forefront as the time to deal with the reality of the genome draws nearer to implementation in practice.

In our opinion, these significant concerns emphasize the importance of a policy framework to guide an evidence-based approach to incorporate WGS technology into health care and public health.  A time is coming when the decision to perform this or that specific DNA test could no longer be relevant.  If DNA testing is needed for any medical reason, pragmatic economics could dictate that WGS is conducted. Patients and their families, under the right scenarios, could benefit from receiving incidental findings with demonstrated clinical utility and with appropriate patient education and counseling.  However, even established tests, such as those for BRCA and Lynch syndrome with demonstrated clinical utility in certain clinical situations, present challenges when testing for WGS in unselected individuals. 

Fortunately, like fairy tale spells, genes do not necessarily determine fate.  However, this is not the time to “hide” important information, supported by evidence of clinical utility, that could be revealed by WGS in health care and disease prevention.  Genetic counselors and other health care providers must be ready to effectively communicate to patients and families what we know and what we don’t know.  Most importantly, we must avoid “spinning wheels” by debating the issues without a firm evidentiary foundation on which to base implementation of WGS in practice.  In order to understand the utility of testing for specific genetic variations in our genome to improve the health of individuals and populations, we must rely on family and population-based research, including clinical trials. 

As for those who have long taken a “wake me when we get there” attitude to genomic medicine: take heart, for the “prince” may be near at hand…

We take the opportunity of March 22, 2013, designated as Lynch Syndrome Awareness Day by 13 U.S. state governors and counting, to highlight state public health genomics programs that are taking innovative approaches to implement evidence-based genomic testing recommendations for hereditary cancer syndromes, including Lynch syndrome. 

Using existing data from central cancer registries, public health programs are bringing attention to potential cases of hereditary cancer syndromes at reporting hospitals and clinics within their states. State health departments provide hospital-specific data reports coupled with provider educational resources, including evidence-based recommendations related to genetic counseling and testing for at-risk individuals. State programs have used cancer registry data to identify thousands of cancer cases that might benefit from genetic evaluation for hereditary breast, ovarian, colorectal and other cancers based on current evidence-based recommendations.

Such was the novel approach developed and implemented by the Michigan Department of Community Health (Michigan DCH) and subsequently carried out by the Genomics Office of the Connecticut Department of Public Health (Connecticut DPH-GO).  The goal was to promote awareness and appropriate use of the 2005 U.S. Preventive Services Task Force recommendation for BRCA genetic counseling and testing related to hereditary breast and ovarian cancer syndrome (HBOC) and the 2009 Evaluation of Genomic Applications in Practice and Prevention Working Group recommendation pertaining to genetic testing for Lynch syndrome.   This public health educational initiative aligned with two new genomics-related Healthy People 2020 objectives.  

Hospital-specific data reports were distributed as follows:

• 434 reports to 151 facilities in Michigan in 2010-11
• 437 reports to 31 facilities in Connecticut in 2012

These reports highlighted the number of early-onset female breast, ovarian, male breast, and multiple primary cancer cases diagnosed over a two-year period — cancers that may be associated with an increased risk of HBOC.  The reports also included the number of colorectal, endometrial, and multiple primary cancer cases diagnosed over a two-year period potentially associated with an increased risk of Lynch syndrome. Michigan DCH has reported back over 15,000 cancer cases based on 2006-2007 registry data, and Connecticut DPH-GO has reported back over 5000 cancer cases based on 2008-2009 data.

Feedback from facilities has been positive and several Michigan facilities have chosen to contact their at-risk patients to collect additional family history information and to ensure that genetic services were received when appropriate. Michigan DCH provided six grand rounds presentations in response to the mailings, whereas Connecticut DPH-GO gave an astounding 23 grand rounds trainings across the state.

Connecticut also distributed cancer genomics educational materials and evidence-based guidelines to nearly 1,000 Connecticut physicians specializing in obstetrics/gynecology or gastroenterology, who are most likely to screen for cancer and identify individuals with family histories of cancer. The packet included a unique tool developed by DPH for healthcare providers – a slide chart containing current, evidence-based referral criteria for HBOC and Lynch syndromes.

This reporting process is thought to be a multi-state success that could be replicated by other state health departments with relatively minimal funding. Raising awareness among healthcare providers will aid in identifying patients with a high-risk personal or family history of cancer and ensure that patients receive genetic services when appropriate. Earlier or more intense cancer screening and surveillance, chemoprevention treatments, or the option of prophylactic surgery may lead to improved health outcomes for patients at increased hereditary risk.

The independent EGAPP working group (EWG) held its 26^th meeting on February 11-12, 2013 at the CDC campus in Atlanta. Highlights included:

• Three EWG recommendation statements on the validity and utility of genetic tests are pending publication on:
  • KRAS, BRAF and other markers involved in EGFR signaling, which are used to inform choice of therapies for metastatic colorectal cancer, recently published in Genetics in Medicine;
  • Genetic risk assessment for type 2 diabetes in general and high-risk populations, recently accepted to Genetics in Medicine ; and
  • PCA3 testing in the diagnosis and management of prostate cancer  based on an evidence review, conducted through the AHRQ Effective Health Care Program (EHC), is being finalized and prepared for peer review.
• The Knowledge Synthesis Center (KSC) presented an update on two systematic reviews:  familial hypercholesterolemia and colorectal cancer screening – the latter topic is being done in conjunction with modeling by NCI /CISNET .

• The EWG heard presentations on available evidence to update two of their previous recommendations: 
  • Can tumor gene expression profiling improve outcomes in patients with breast cancer?; and
  • Genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives.  The evidence heard on this topic was to consider the addition of endometrial cancer to the overall Lynch Syndrome recommendation. 

In addition to issuing recommendation statements, a central mission of the EWG is to develop and test new methods for evidence-based evaluation of genomic tests.  In keeping with this aim, the KSC, along with several EWG members, have submitted a manuscript for publication in Genetics in Medicine entitled “Description and Pilot Results from a Novel Method for Evaluating Return of Incidental Findings from Next Generation Sequencing Technologies” based on methods and considerations for “binning findings from whole genome sequencing”. The manuscript has been accepted with minor revisions. 

Criticisms of evidence-based processes as requiring too much time, labor and expense are all too common. The experience of the EGAPP initiative has taught us that while discovery-based knowledge and resulting hype surrounding genomic applications does evolve and accumulate quite rapidly, quality information supporting the validity and utility of using these applications in health care typically does not. To address these concerns, the past and present EWG members are in the final stages of drafting a manuscript entitled, “The EGAPP Initiative:  Lessons Learned” in an effort to inform stakeholders of the possibilities and pitfalls of their efforts. 

The next EGAPP Working Group meeting will be held on May 13-14, 2013.

Population screening for disease  is a concept that has been around for many decades. Its main purpose is early detection and treatment of asymptomatic disease, or risk assessment and prevention of future disease, in order to improve health outcomes in individuals and populations. Examples include mammography in breast cancer screening and colonoscopy in colorectal cancer screening. Principles and criteria for population screening programs have been developed by many organizations and have evolved over time. These principles ensure that the benefits of screening programs outweigh potential harms such as overdiagnosis, inappropriate interventions and anxiety.

A criticism often leveled against criteria for population screening is that screening guidelines typically apply to the “average” person in the population and may not be relevant to subgroups of the population with differing levels of risk.  Advances in genomics promise more targeted or personalized approaches to screening such as stratifying the population on the basis of differing levels of genetic risks.  For example, in breast cancer screening, the United States Preventive Services Task Force currently recommends biennial screening mammography for women aged 50 to 74 years. However, they do acknowledge that the decision to start regular screening mammography before the age of 50 years should be an individual one and take patient context into account, including the patient’s other risk factors, as well as values regarding specific benefits and harms. This second recommendation reflects the continued debate and uncertainty about the balance of benefits and risks of breast cancer screening under age 50.

Could advances in genomics improve the benefits of population screening beyond “average risk” screening guidelines by stratifying the population into high risk subgroups that require earlier or more frequent screening, and lower risk subgroups that require no or less frequent screenings. Hereditary breast and ovarian cancer due to mutations in BRCA genes provides an example of a high risk subgroup of the population that may require more targeted interventions. Currently, the U.S. Preventive Services Task Force recommends that all women with certain family history patterns for breast and ovarian cancer be offered genetic counseling and evaluation for BRCA testing in order to reduce morbidity and mortality from breast and ovarian cancer.

Although BRCA mutations greatly increase the risk of breast and ovarian cancer in affected persons, they still account for a small fraction of cases of breast cancer in the population. However, there are many more genes with smaller disease risk that could account for much larger proportion of breast cancer. Can we construct a rational scenario for using such genetic information to guide breast screening recommendations that are largely based on age? In the online issue of Genetics in Medicine, Chowdhury et al. report on the recommendations of multidisciplinary expert workshops convened by the Foundation for Genomics and Population Health in the United Kingdom. Participants examined scientific, ethical and logistical aspects of personalized population screening for prostate and breast cancer based on polygenic susceptibility. The authors recognized the promise of genetic stratification in population screening. For example, instead of only using an age cutoff for screening, the combination of age and genetic risk profile can theoretically provide a more efficient screening program. However, key issues need to be addressed before genetic stratification can be implemented in practice.

In our accompanying commentary, we elaborate on some of the issues that need to be answered before testing for multiple genes can be integrated into population screening. These include 1) the absence of credible epidemiological data on genetic and environmental  risk factors on disease occurrence in the population to be tested; 2) the absence of information on whether or not genes can identify individuals who will actually benefit from early detection and can benefit from earlier interventions; 3) the absence of information on benefits, harms and costs of using different interventions at different levels of genetic risk;  4) the absence of information on acceptability of genetic stratification by the population; 5)  the lack of readiness of the healthcare and public health systems in integrating such information in practice.

Population screening for rare genetic diseases with high disease risk and evidence-based  interventions (such as newborn screening) will continue to be a mainstay for genetic screening for a while. However, technological developments will drive the interest in using genetic testing for multiple genes to stratify risk in population screening programs and for personal genomic tests. As Dent et al recently commented “stratified screening based on genetic testing is a radically new approach to prevention. Various organizational issues would need to be considered before it could be introduced, and a number of questions require further research.”  In the meantime, full engagement of the scientific community, clinical and public health practice, consumers and policy makers is needed to prepare for the evidence-based integration of genomic information into health care and disease prevention. 

We invite our readers’ comments and opinions regarding the appropriate role of genetic testing in population screening for various diseases.

Two non-profit foundations with distinct missions recently announced that they are joining forces to support polio eradication. The Bill & Melinda Gates Foundation (BMGF) supports global health programs; the Jeffrey Modell Foundation (JMF) advocates for early diagnosis and treatment of  genetic immunodeficiency disorders. How did these organizations find common cause? 

During the last two decades, surveillance and strategic vaccination campaigns deployed by the Global Polio Eradication Initiative have reduced polio incidence worldwide by 99.8 percent. Wild poliovirus cases are now uncommon, with fewer than 250 new cases reported wordwide during 2012. Endemic transmission is now limited to small areas of just three countries—Afghanistan, Nigeria, and Pakistan.

Oral polio vaccine (OPV) is a live, attenuated vaccine that is used for eradication because it is effective, inexpensive, and easy to administer. When persons with immune deficiencies are directly or indirectly exposed to OPV-related viruses, long-term infections may rarely arise and lead to vaccine-derived polioviruses (VDPVs).

Persons with a genetic primary immunodeficiency disorder (PI, see Box) can carry replicating VDPVs in their intestines and potentially transmit them to their contacts. Reports of such instances are rare and the underlying PI is often detected only after the onset of paralytic polio; however, additional cases have been identified by intensified surveillance and special studies set up by CDC and the World Health Organization (WHO).

A CDC-funded study in Bangladesh recently demonstrated that it is feasible to identify children with PI by screening with a clinical case definition (based on criteria developed by the Jeffrey Modell Foundation), followed by age-specific determination of quantitative immunoglobulin (QIG) levels. Six of the 13 children who met the clinical case definition had QIGs that confirmed the diagnosis of PI. Stool specimens that were obtained from four of these six children tested negative for polio vaccine viruses. The authors recommended expanding surveillance for PI and regularly testing vaccinated persons with PI for poliovirus excretion.

Polio eradication is an important public health priority and an ambitious goal: only one other infectious disease of humans—smallpox—has ever been eradicated from the world’s population. The final push toward polio eradication requires a coordinated, all-out effort by international groups and national governments, public agencies and private foundations. The successful strategy will find synergy between population-based surveillance and case-finding, mass vaccination and clinical screening. Although OPV will be phased out once the goal of polio eradication is reached, any long-term infections in PI patients will require special attention.

British epidemiologist Geoffrey Rose inspired a generation of public health workers when he contrasted population-based with individual risk-based strategies in his essay, “Sick individuals and sick populations”:

The ‘high-risk’ strategy of prevention is an interim expedient, needed in order to protect susceptible individuals, but only for so long as the underlying causes of incidence remain unknown or uncontrollable; if causes can be removed, susceptibility ceases to matter.

The goal of eradicating polio, however, clearly calls for both strategies. Population-wide vaccination programs are delivered by vaccinating individuals—thereby protecting those who are vaccinated, their close contacts, and the whole population through herd immunity. In many areas where wild poliovirus transmission has been interrupted, like Bangladesh, the role of PI in polio eradication has clearly begun to matter. The BGMF has supported polio eradication efforts for years; however, the Jeffrey Modell Foundation is a new partner in a collaboration with CDC, WHO and the Task Force for Global Health that will broaden surveillance for VDPV in persons with PI within the Jeffrey Modell Foundation clinical network. Any long-term VDPV infections that are found are potentially treatable with new antiviral drugs currently under development.

So where are we 15 years later? With rapid improvements in technology, we are seeing the leading edge for applications of whole genome sequencing in health practice both for the detection and control of infectious disease outbreaks, and for the identification of people with increased risk for a wide variety of rare and common diseases of public health significance.  Although much of the field will be a work in progress for quite some time, an increasing number of genomic applications can actually save lives now by improving health and preventing disease in the US and worldwide. As the genomics revolution turned into an evolution, it is no longer the case that genomics is “not ready for prime time” for clinical and public health use. Nevertheless, public health’s initially understandable but still persisting “wait and see” attitude needs to change.

To help with the integration of the tools of genomics in health practice, in 2012, the CDC Office of Public Health Genomics developed an evidence-based classification schema for human genomic applications in medical and population settings.  The schema takes a population perspective for an emerging role for public health programs to supplement clinical practice. One may be surprised to see on this list several applications that are supported by recommendations from evidence panels. In addition to newborn screening, which is the largest public health genetics program in the world, an increasing number of applications are being regularly added to the list. Newborn screening in the United States leads to the diagnosis and management of more than 12,000 newborns every year with one of 31 disorders recommended for the uniform newborn screening panel. Additionally, there are currently about 2 million persons in the US affected with one of three genetic conditions that put them at increased risk for early heart attacks and cancer.  Most affected individuals are not aware of their risk and there are evidence-based interventions that can significantly reduce their risk. A combined public health and healthcare approach using cascade screening could provide access to genetic evaluation and preventive interventions in relatives of affected patients. These applications are only the tip of the iceberg for what’s to come in the next decade. For example, there are genomic tests in clinical practice for more than 2500 diseases, more than 100 pharmacogenomic tests that have been suggested for use for a wide variety of diseases, emerging prenatal tests, enhanced newborn screening panels, a plethora of genome-based biomarkers, as well as the advent of whole genome sequencing for both pathogens and humans.

The next 5 years will require a closer collaboration among public health, healthcare organizations and the private sector to implement what we know to benefit populations. The public health community can serve as the honest broker for rapidly emerging applications and technologies, and help ensure that the tools of public health science are used appropriately to evaluate the health impact of genomics at the individual and population levels.

There are more than 2500 diseases for which genetic testing is currently available. Most of these diseases are individually rare conditions but collectively affect millions of individuals and families worldwide. Genetic diseases are usually caused by mutations in one or a few genes that may confer a high risk of illness, disability and early death. Immediate relatives of affected people can be at highest risk for these diseases.   Rapid advances in genomics, including whole genome sequencing, are leading to more accurate diagnosis, early detection and carrier testing for these diseases.  Genetic counseling provides information for decision making by affected people and their families. 

In 2012, the CDC Office of Public Health Genomics developed a three tier evidence-based classification schema for genomic applications in public health and clinical settings. Our online table is intended to promote conversation and stimulate input from providers, public health practitioners and consumers alike.  The schema takes a population perspective for an emerging role  for public health programs to supplement clinical practice. Tier 1 includes applications supported by recommendations from evidence panels that used systematic reviews to assess the balance of benefits and harms from testing and interventions. In addition to newborn screening, which is the largest public health genetics program in the world, we highlight three tier 1 diseases-hereditary breast and ovarian cancer, Lynch syndrome and familial hypercholesterolemia as candidates for existing public health programs to identify people at increased genetic risk for disease through  “cascade genetic screening.” 

Cascade screening is an active process to find relatives of persons affected with certain genetic conditions, for which interventions exist that that can save lives.  In the recent video, “Cascade genetic screening and public health practice: an idea whose time has come”, the case was made that 2 million people in the United States are affected with one of the three genetic conditions mentioned above. Existing public health programs at the federal and state levels (notably cancer and heart disease programs) can partner with clinical medicine and other stakeholders to develop policy, educational and surveillance-based interventions for these conditions. Since 2011, public health programs in hereditary breast and ovarian cancer have been under way in Michigan, Oregon and Georgia.

What about the role of public health for the vast majority of other genetic conditions, where cascade screening is not a tier 1 application?  For many individual rare disorders, there may never be sufficient evidence to meet the highest evidentiary criteria of major guideline-producing organizations using traditional evaluation methods.  Clearly, unbiased, accessible information about genetic conditions is important for affected individuals and their relatives. For example, CDC has developed and sponsored educational and informational programs around selected genetic conditions, such as Duchenne Muscular Dystrophy, Fragile X Syndrome, and Primary Immune Deficiency Disorders. Many community programs exist both within and outside the US, a field sometimes referred as Community Genetics.  Information could be  collected through the use of population based registries that could show impact of these programs at the individual, family and population levels. 

We will continue to monitor the evolving scientific evidence to include more genetic conditions in tier 1 applications for population and/or family-based cascade screening programs. We invite our readers’ comments and input on what public health practice can do for individuals and families affected with genetic diseases.

A Working Meeting and an Action Plan
to Save Lives Now

Nearly 2 million Americans are affected by one of three genetic conditions with a strong risk of early morbidity and mortality: BRCA 1/2 and hereditary breast and ovarian cancer; Lynch syndrome and colorectal , endometrial and ovarian cancer; and familial hypercholesterolemia and early cardiovascular events.  At present these conditions are poorly identified by the healthcare system but evidence based recommendations are available to prevent disease and improve health.    

Opening speaker, Dr. Ursula Bauer Director, NCCDPHP discusses a point later in the day with Dr. Khoury, OPHG Director

On September 7, 2012, eighty experts and stakeholders representing federal, state and local public health agencies, clinicians, key advocates and community leaders came together at CDC’s Roybal headquarters in Atlanta to develop a plan to use evidence based “Tier I” interventions to reduce morbidity and mortality from these three conditions.  The event was organized by the CDC Office of Public Health Genomics (OPHG) with help from the University of Michigan Center for Public Health and Community Genomics, Genetic Alliance, and a multi-disciplinary planning committee. The full meeting report is published on the Genomics Forum website and is available for   download at  http://genomicsforum.org/editoruploads/ActionstoSaveLivesNowReport.pdf   

The day’s work centered around: reviewing the evidence of effectiveness in implementing available interventions; identifying opportunities, strategies, and models; and identifying the means to achieve success for these new and cost effective public health programs.  

Using the “Health Impact Pyramid” as a guide, participants discussed various steps which could be taken, given challenges and opportunities for improvement. Particular emphasis shpuld be given to actions lower on the pyramid, such as policy changes (for example: coverage/care for Tier 1 applications). Interventions at this level have more population impact because they change the context to make people’s default decisions healthy.

Said Deb Duquette MS, CGC of the Michigan Department of Community Health, one of several state representatives present at the event,”Clearly work to inform policy change is critical for Tier 1 programs and has been a major part of our success in Michigan. This was particularly true where healthcare coverage for the USPSTF BRCA 1/2 recommendation was expanded to seven million people in our state.  The public health impact for the dollar is large in the policy area and this model can be applied in many other states.”

1. Incorporate and build on the previous success of state public health genomics programs, in particular by employing  new policy implementation approaches;
2.  Develop and use standardized protocols as a guide for Tier 1 program activities;
3.  Develop and distribute standardized communication materials for Tier 1 applications including educational materials for patients, providers, and public health practitioners;
4.  Develop and use standardized surveillance indicators, such as those for HP2020  to measure success and integrate synergistically with provider/payer systems;
5.  Collaborate and share lessons learned with other states and partners such as what is being done with the  Lynch Syndrome Screening Network (LSSN);
6. Conduct cascade screening (identifying relatives at risk from case patients) pilot projects and consider the scalability and cost effectiveness of broader  programs that use it ;
7.  Build strong partnerships toward mutual goals which include healthcare payers, healthcare providers, advocacy groups, and other key stakeholders;
8.  Stay abreast of changes in the field as new applications with sufficient evidence for implementation become available.

To follow up on the event’s success, a “Tier 1 Toolkit” is now being developed which will provide the tools and educational resource identified during the event as keys to progress. This resource will be available on CDC’s website before the end of this year, and will help states to overcome the unique challenges in this arena, establish key healthcare and payer partnerships, and take action to save lives now using Tier 1 public health genomics applications.

The event’s Patient and Community Perspectives Panel included key leaders (from left to right): Katherine Wilemon, Founder and President, the FH (Familial Hypercholesterolemia) Foundation; Sue Friedman, DVM – Executive Director, FORCE (Facing Our Risk of Cancer Empowered); Cristi Radford, MS, CGC – Lynch Syndrome International / Moffitt Cancer Center; Rochelle Shoretz, JD – Executive Director, Sharsheret: Your Jewish Community Facing Breast Cancer; Sabrina Ford, PhD – Department of Obstetrics, Gynecology & Reproductive Biology, Michigan State University; and Winona Hollins Hauge, MSW, LCSW – Fred Hutchinson Cancer Center, Governor’s Interagency Council for Health Equity (Washington State), National Community Committee Genomics SPIG/UW HPRC.

New Strategies in Public Health Genomics:  Actions to Save Lives Now
Atlanta, Georgia
September 7, 2012