The successful sequencing of the human genome, completed just 13 years ago, has opened the door to a broad range of medical opportunities and challenges.
The ability to gain health information from such tests and then apply it to diagnostics and therapeutics has already fostered enormous changes in clinical medicine, and has ushered in the era of precision medicine.
If the current pace of development in this area continues, genetic testing is likely to play an increasingly pivotal role in clinical medicine in the near future.
Genetic testing is also assuming a much higher profile in life and health insurance and could play a pivotal role here as well. Information from genetic tests has the potential to improve population mortality and morbidity experience, but there are many challenges for insurers in using such information. At this point, many countries do not permit genetic test results to be used in underwriting, even when the results are shared with an insurer. In addition, the widening ability of individuals to order their own genetic tests is generating a growing asymmetry of information which may create added challenges.
The impact of genetic testing on the insurance industry will continue to be the topic of actuarial research for some time, as insurers address this issue in their pricing and valuation. Insurance product development opportunities may also emerge to capitalize upon this medical trend in genetics that would benefit both the public and the insurance industry.
Genetic Testing: The Science, Validity, and Utility
Genetic information for each individual is contained within the 23 chromosome pairs that are in nearly every cell of the human body. Each parent contributes one of the two DNA chains comprising each chromosome, and every chromosome contains a total of three billion base pairs, or approximately 23,000 genes. These genes make up only 2% of our DNA. The rest of the noncoding DNA regulates gene expression.
Research has shown that all humans are about 99.5% the same genetically (Levy et al., 2007), and twin studies have shown that approximately 25% to 50% of morbidity and mortality differences from person to person are due to genetic factors (Christensen and Vaupel, 1996; Polderman et al., 2015). Mutations in human DNA can lead either to disease or to protection from disease, or might have little to no impact at all. The rest of the variance in disease rates is due to environmental and lifestyle factors.
There has been a rapid increase in public access to genetic testing either through doctors, employee health programs, or via direct-to-consumer genetic testing kits. Some countries have banned direct-to-consumer genetic testing, requiring genetic tests to be ordered by a physician who can then explain and interpret the test results for patients. Clinically, most genetic tests are done for patients whose families have a history of a particular disease.
Not all genetic tests are the same. Inexpensive genome wide association studies (GWAS) use microarray (gene chip) technology to examine a genome-wide set of genetic variants and produce genotypes. Genotyping then looks for single nucleotide polymorphisms (SNPs) in DNA that are associated with an increased predisposition to develop a disease or with side effect propensity for certain drugs.
Other sequencing methods include whole genome sequencing (WGS), which decodes every single base pair in the DNA strands, and whole exome sequencing (WES), which only decodes the protein-producing genes within a chromosome. If a person has symptoms or a family history of an illness, genetic tests can be ordered that look for specific mutations associated with that impairment without sequencing the entire genome. This can help the diagnosis and prognostication of a disease. The cost of commercially available genetic tests can range from US$250 to US$4,500, depending on testing methodology and completeness of the assay.
Genetic testing can also be done on genes in cancer cells. This has enabled the discovery of new targeted biological anti-cancer therapies, which have been shown to improve cancer survival in the approximately 10% to 15% of cancer patients who have advanced disease.
A recent study reported that 91% of cancer patients had actionable mutations (that is, mutations with significant diagnostic, prognostic or therapeutic implications for cancer patients and their families) and that 10% of their treatment plans were altered as a result of genetic testing of their cancer genome done at the time of the cancer diagnosis (Uzilov, 2016). Unfortunately, these new targeted cancer medications are currently very expensive and usually only extend life expectancy marginally.
As with all medical tests, genetic tests are not perfect. There can be false positive and false negative results. Whether a genetic test is applicable in a given clinical situation depends on that test’s analytical validity, clinical validity, and clinical utility. In terms of analytical and clinical validity, genetic tests can reliably find mutations, but as genotyping panels do not test for all types of genetic mutations, the possibility of false negative results exists. Having a mutation also does not necessarily mean high penetrance (i.e., the chance the associated disease will develop). For example, genotyping results for multifactorial multi-gene disorders such as diabetes and cardiovascular disease are associated with a relatively small increase in the relative risk of developing these diseases.
Clinical utility, a major area of ongoing research, implies whether knowing a patient has a specific mutation might change how a doctor manages that patient, such as motivating him or her to change behaviors or instituting preventative medicine strategies that might materially improve clinical outcomes. For example, according to a 2013 study, approximately 3% of adults carry high-penetrance actionable pathogenic or likely pathogenic genetic mutations, where doctors can change patient care to prevent disease (Dorschner et al., 2013). Many critics of genetic testing argue that evidence is not yet strong enough to use genetic information in clinical care unless there is a strong adverse family history of a particular disease.
Genetics is also the backbone of the growing specialty of precision medicine and specifically of pharmacogenomics, which is the study of how genes affect a person’s response to drugs, enabling the provision of the right drug, at the right dose, at the right time. Currently, 7% of all of the 1,200 medications ever approved by the FDA, and 13 of the 45 new drugs approved by FDA in 2015, are considered to be “personalized medicines” where drug-gene interaction plays an important role (Relling et al., 2015). As serious adverse reaction to medications is common in clinical medicine, increased use of pharmacogenomics to enable greater precision in prescribing and treatment could lead to significant decreases in drug side effects, improved disease outcomes, and ultimately, improved morbidity and mortality. This is extremely relevant, given that medical error has been reported as the third leading cause of death in the U.S. (Makary and Daniel, 2016).
Genetic tests are also being used to replace certain invasive diagnostic tests, which is affecting how insurers assess living benefit claims.
An exciting new tool in genetic research is CRISPR (clustered regularly interspaced short palindromic repeats) gene editing. This lets researchers slice a genome at a selected site. It is anticipated that this tool will enable not just the isolation of a specific section of a gene for study, but also the eventual possibility of treating a disease via gene editing; i.e., removing a disease-generating genetic mutation and replacing that section with healthy sequences.
Risks and Benefits of Genetic Testing for Insurers
Genetic testing is an emotionally charged and controversial topic for the public, for lawmakers, and for the insurance industry. For insurers, several possible risks and benefits exist in its use.Read More +