Genetics and Genomics: A Look at the Present and Not-So-Distant Future

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 Kimberly Kaphingst, PhD

From the February 2012 issue of YWBCP magazine
By Kimberly Kaphingst, ScD
Assistant Professor of Public Health Sciences
Washington University School of medicine

This issue of YWBCP is focused on healthy survivorship. You may ask, what does genetics have to do with survivorship? As it turns out, a great deal. Genetic information is currently used to guide treatment at diagnosis and medical follow-up throughout survivorship. As research and technology advance, genetics and genomics information will continue to be essential in directing care.

Before we dig too deep, let’s consider two definitions. As a general rule, genetics is the study of single genes. In contrast, genomics is the evaluation of all of the genes that comprise the genome (or a person’s entire genetic makeup) and the interactions among them. Both types of information are needed to provide the most comprehensive understanding of a specific disease, like breast cancer. A scientist can discover all there is to know about a gene, but knowing how a gene interacts with other genes is equally essential. Searching genomes to identify genetic differences among people with a disease is extremely helpful, but learning the details about a specific gene that causes a disease is also vital. Genomics cannot replace genetics or vice versa.

Let’s first consider how genetics is used today in the care of people diagnosed with cancer. There are three major areas of focus.

  • Tumor genetics is the evaluation of genes within a tumor. This type of evaluation is currently used to characterize a tumor and identify the most appropriate treatment for that specific tumor. Oncotype is a test that examines 21 genes in women with early stage, node-negative, estrogen-receptor-positive breast tumors. It predicts the likelihood of a recurrence and thus provides data to determine if chemotherapy is needed.
  • Pharmocogenetics is the study of how natural gene variations that exist among people impact the processing of certain drugs and their byproducts. Determining how different gene variations influence drug metabolism is an intense area of research. Certainly you would not want to receive a drug if you were not going to benefit from taking it.
  • Inherited or germline genetics refers to the study of genes that have been inherited from your parents and are shared among other family members. Many young women diagnosed with breast cancer have had partial or complete testing of genes like BRCA1, p53 or pten because of their personal and family history of cancer. The importance of knowing this information is that long-term medical follow-up of women with an inherited gene mutation differs compared to survivors who do not have a mutation.

How will the fields of genetics and genomics evolve over time and how will these scientific advances impact the care of young women with breast cancer and their families?

Let’s focus on inherited or germline genetics. In the near future, young women with breast cancer will not be offered genetic testing for only one or two genes but rather testing for a panel of 25 to 30 genes will soon be performed. These panels will be comprised of genes that are all associated with an increased risk of developing cancer. Testing for multiple genes will identify more women with an inherited gene mutation and thus allow more women to potentially benefit from targeted treatment and follow-up. Gene panels have already been developed for colon cancer and most likely will be instituted for breast cancer after patents on the BRCA1 and BRCA2 genes expire.

What if we take testing a step further and consider analysis of a person’s entire genetic makeup? As a result of recent technological advances, a person’s genome can now be evaluated quickly and at a lower cost. Timothy Ley, MD, at Washington University was the first scientist to publish the entire genome of a person diagnosed with cancer. It took several months to complete at a cost well over $1 million. Now, a person’s genome can be evaluated within days at a cost less than $10,000. Compare this cost to the current charges for BRCA1 and BRCA2 gene analyses, which exceed $4,000.

In the not-so-distant future, people diagnosed with cancer will soon have their entire genomes analyzed to determine their treatment and medical follow-up. Imagine having more than
20,000 genes analyzed within a matter of days from your diagnosis. Genome analysis performed for the purpose of clinical treatment decisions is currently being offered in very limited settings but will become more widely available.

Making genome analysis available to everyone is an exciting possibility. However, critical questions remain. With the analysis of over 20,000 genes, thousands of gene variations will be identified. The first key issue to address will be to determine which variations are associated with a disease and which are benign. Our lack of knowledge of which gene variations are linked to disease is a prime reason why genome analysis has not yet been widely used in the care of people with cancer – or for people with any specific disease.

We must also consider the communication, behavioral and ethical issues that arise from the field
of genomics.

  • How do healthcare providers communicate information about a person’s entire genome? Did you feel overwhelmed when you received information about your cancer diagnosis? Just imagine how difficult it might be to process information about your genome.
  • When is the most appropriate time to communicate complex genome results? At the time of diagnosis, after treatment is completed or several years afterward?
  • What information is communicated and who makes that decision? If genome testing was performed because of your diagnosis of breast cancer at age 29, do you want to know if you have an increased risk to develop heart disease or dementia? Should you know?
  • How will you incorporate the information in your personal health behavior? Numerous studies have demonstrated a lack of progress in achieving positive behavioral health changes based on population-based recommendations. For example, did you change your eating habits after the food pyramid was published? The question of whether people will be more likely to change their personal behaviors based on genomic information remains to be answered.
  • With whom do you share your genome results? Do you have an ethical obligation to share the information with your children, siblings or extended family members?

These are just a few of the complex questions that have not been adequately studied and that need to be addressed before genome analysis is routinely used in clinical decisions. As an educated healthcare consumer, it will be essential for you to share your opinions and insights as to how these questions should be answered, now and in the future.

In A Tale of Two Cities, Charles Dickens wrote, “It was the best of times, it was the worst of times, it was the age of wisdom, it was the age of foolishness…we had everything before us, we had nothing before us.” The contrasts Dickens described long ago seem incredibly relevant as we consider the research and technological advances of the day. Genetics and genomics will continue to bring significant medical advances, but let us proceed wisely and with proper intent to ensure it is the best of times for all.