Seeing the Forest Through the Trees: Dr. Wendy Chung on Genetics and Cancer

Reflections is a series featuring Columbia cancer experts, looking back at how far we’ve come in advancing and impacting change in research, treatment, care, and survivorship, and their perspectives on what lies ahead.

April 29, 2022

On June 13, 2013, the U.S. Supreme Court unanimously ruled that human genes cannot be patented, in a case against Myriad Genetics brought on behalf of the ACLU and a group of interested parties, including Columbia University geneticist Dr. Wendy Chung. Dr. Chung saw the negative impact exclusive testing with a single lab had on patients, sometimes barring them access to genetic testing that could arm them with decision-making information about their diagnosis, treatment and care. Myriad held the exclusive licenses to the patents on the BRCA1 and BRCA2 genes, the most commonly affected genes in hereditary breast and ovarian cancer.

At the time of the ruling, Dr. Chung said, “This decision means we are not going to be impeded in giving full information to our patients about all of their genes.” Reflecting on past progress and what is to come, Dr. Chung discusses the ever-evolving field of genetic testing and research, zeroing in on cancer.

What was the genetics field like at the start of your career? 

Over the course of my career, the changes we’ve seen are profound, because when we started doing this, we didn't know about any cancer susceptibility genes, like BRCA1 or BRCA2. We knew that they must exist because we'd see families that seemed to have very strong family histories of cancer, and usually these were particular types of cancers, such as breast cancer running in the family or colon cancer, but we didn’t know the exact genes or genetic variants. In my lifetime, I've seen first, the identification of those genes, and then second, the clinical implementation of genetic testing. 

Let’s dive into that first part. Which genes were first identified and how did that shape the field?

Most people are familiar with BRCA1 and BRCA2 genes, whether it's because they've heard of the Angelina Jolie story or they themselves know of someone with an increased cancer risk due to these genes. They were somewhat of a misnomer at the beginning, because they were named BRCA1 and BRCA2 for breast cancer 1 and 2, but they truly are breast and ovarian cancer genes. A lot of the infrastructure that was built around clinical implementation was built around those two genes, because those were the genes we knew about first and it was clear from a clinical standpoint what to do with that information. There were women who thought about having surgeries to reduce their cancer risk, whether that was a mastectomy [the surgical removal of one or both breasts] or oophorectomy [the removal of one or both ovaries]. We’ve since developed programs to help those women make important decisions based on knowledge of their cancer risk profile. This ability really can be life-changing and lifesaving. 

But those with mutated BRCA1 or BRCA2 genes aren’t in fact the majority of people who either get breast cancer or who are at risk for breast cancer. They're the peak of risk; having one of these genes puts you at the highest risk. We've since identified other genes that instead of increasing cancer risk by ten-fold, they might increase risk by two-fold. There's quite a different decision that patients make when you're at a two-fold increased risk rather than ten-fold. We've started building tailored care models, ways of educating people and thinking about different treatment and care management options based on a person’s individual risk. 

So, now we’re getting into how genetic testing has been clinically implemented. Can you elaborate? 

Yes, the second big wave in the clinical implementation of genetic testing was thinking about how you start to then integrate that information into clinical care, into routinization in terms of being able to provide a comprehensive genomic assessment for each patient diagnosed with cancer or at risk for cancer to tailor their treatment and care. For me, this second wave has really been for two different clinical use cases. One is people diagnosed with cancer and trying to think about their cancer management specifically. The other clinical use cases are people who don't yet have cancer, and hopefully, never will have cancer, but where we use this information in risk stratification to think about how to either reduce risk or screen for cancer and tailor that plan based on the individual and specific factors, everything from gender to stage in life to genetic and non-genetic risk factors and putting that all together.

Photo of physician and pediatric patient in hospital setting.
Dr. Wendy Chung is a leading clinical and molecular geneticist and physician, and the Kennedy Family Professor of Pediatrics (in Medicine). (Courtesy of Columbia University Irving Medical Center)

For instance, within the Jewish community, we know that 1 in 40 people has a mutation in either the BRCA1 or BRCA2 genes. We have a very accurate understanding of the cancer risk profiles for this population. We even have curves to know over the life course when that risk starts becoming higher. So, this first wave of progress has been powerful, where we identified the BRCA1 and BRCA2 genes, knowing the cancers associated with them, knowing that in particular, Jewish communities were at higher risk. The same storyline has happened for colon cancer. Realizing that there are genes for colon cancer, we’ve routinized screening to identify which individuals with colon cancer may have genes that increase their risk of other types of gastrointestinal cancer, or uterine or ovarian cancer for the women. We’re able to really understand the full cancer risk for them and their families.

Where do we go from there? 

We're just starting to get into a brand-new era, where historically we've done genetic testing for genes, like BRCA1 and BRCA2, that have a remarkably high penetrance, or in other words, very high likelihood that someone will get cancer. We’re now getting to the point where we can use genetic and non-genetic information to come up with better cancer risk stratification for a larger number of people. That's a new concept in terms of thinking about not just individual genes or variants, but looking at something like 500 different genes or variants, and in a mathematical way, being able to look at the combination of those in an individual. We can take all of that data and apply algorithms to understand the cancer risk of that individual based on all those unique genetic contributions. We can now see not just one tree, but the entire forest.

Is that essentially what precision prevention is? Can you tell us a bit more?

Yes, this is precision prevention. It’s information about your individual risk profile in sufficient detail so you can come up with a strategy to mitigate your risk and/or detect cancer at an early treatable stage. We can model the effect of various interventions including exercise, diet, smoking, and show someone how they can bend their personal curve to reduce their cancer risk.

Switching gears. What’s your take on the DNA consumer market, which has taken off recently? Are you for these home-based genetics testing options? 

One of my core beliefs is that people should be empowered to get information they need and to be able to make rational decisions about their health. The problem is that some of the direct-to-consumer products may not be clear in what they're providing. You might think you're getting something about your breast cancer risk stratification, but there's little scientific or medical information content in there. I worry about people who think they might have “clean” genes after taking a home-based genetics test and think they don’t have to worry about going for their annual mammogram or having a colonoscopy. If you want to find your long-lost relatives or if you’re adopted and you don't know your family’s origin, then some of these consumer DNA products might be a good way to do that. Using these products to trace your ancestry and your roots can be useful, but don’t depend on them for medical guidance.

What made the greatest impact on the field to date? 

The Human Genome Project. I’m smiling because we just had a virtual session with President Clinton, [former NIH directors] Francis Collins and Harold Varmus, and Donna Shalala [former U.S. Secretary of Health and Human Services]. We had a whole session, thinking back to the Clinton era and reflecting on this major accomplishment. Bill Clinton was a strong advocate for the Human Genome Project, and it was during his administration that the first draft was completed.

The Human Genome Project fueled everything that I've talked about –being able to find genes, identify genes, and being able to do better cancer risk stratification. That was one of the best investments we made as a scientific community and has been hugely impactful.

What’s the next frontier to explore? 

We’ve taken a few baby steps, but I want to emphasize that right now my field is not fair and is not equitable. What I mean by that is we serve a wonderfully rich and diverse community here at the Herbert Irving Comprehensive Cancer Center and with the genetic testing that we do I cannot give equally useful information to all the patients who come to see me. If you happen to be of European ancestry, I can give you much better information than if you come to me and your roots are from Nigeria. The fundamental problem is that we don't have equal representation in the genetic data that we have to interpret what the DNA means. Right now, 80% of the genetic data we have on “average people” comes from individuals that represent 20% of the world's population. We should have 80% from 80%. Anyone other than individuals of European ancestry are underrepresented. To me, that is fundamentally not fair and not equitable. We have a lot of work to do there. 

References

Wendy K. Chung, MD, is a clinical and molecular geneticist and physician. She is the Kennedy Family Professor of Pediatrics (in Medicine) at Columbia University Vagelos College of Physicians and Surgeons and division chief of Clinical Genetics at the Department of Pediatrics. At the Herbert Irving Comprehensive Cancer Center (HICCC) at NewYork-Presbyterian/Columbia University Irving Medical Center, she serves as associate director for Education and Training and is a member of the HICCC’s Cancer Genomics and Epigenomics research program