Why me?: How hereditary cancer testing can provide answers for patients with some blood cancers

By Dr. Amy Trottier*

There’s one question that almost every patient that walks into my clinic has, which I sadly don’t always have an answer for: why me?

As a hematologist, I know that the lack of answers to this question weighs heavily on my patients and their family members. That’s why I’ve always been interested in researching the mechanisms that cause individuals to develop blood cancer. In many cases, the answers remain painfully elusive. For some patients, though, the answer to this question is becoming clearer and can be found in a place where doctors haven’t always been looking: their family tree.  

The understanding that some blood cancers are hereditary is rather new—at least to science. Not too long ago, when I was in medical school, I was told that blood cancers were not hereditary. This clashed with the reality I later experienced. While completing my hematology training in Calgary, I began seeing families with multiple cases of blood cancer—including patients diagnosed in their 20s and 30s. 

These were clear red flags that suggested a hereditary cause, and which made me question what I had learned at medical school. This led me to pursue a post-doctoral fellowship at the University of Chicago focused on translational research into the genetic origins of blood cancers, where I began actively investigating the “why” behind these cases. 

Of course, science was just catching up with what affected families knew for many years—that something was not right in their genes. 

The transition has been rapid. Today, all major clinical guidelines have sections devoted to the hereditary components of blood cancers. Now, continued research is crucial to understand why this is happening, who is at risk, and how we can improve both early detection and outcomes for patients who do develop these cancers.

Using hereditary cancer testing to inform safe and effective care

When I came back to Canada as a clinician-researcher with Nova Scotia Health and Dalhousie University, my goal was not only to continue my research into hereditary blood cancers, but also to provide opportunities for patients and their families to access genetic testing that could reveal whether they were at a higher genetic risk of these and other cancers. In 2020, I’m proud to say that I opened the first hereditary hematologic malignancy risk clinic in Canada. 

Our clinic is addressing challenges and barriers on multiple fronts, helping to move the needle on both research and clinical impact ethically and through a patient-centred approach.

As I noted above, this type of hereditary exploration can have important impacts not only for people currently experiencing cancer, but also for their families. A story about one of my patients exemplifies this very well.

This patient—let’s call him John—was diagnosed with acute myeloid leukemia (AML) at 41 years old. I saw John at my clinic in Halifax, and genetic testing revealed that he had an inherited genetic alteration recently found to be associated with this type of cancer.

Following standard treatment, John’s cancer went into remission. However, he unfortunately relapsed less than a year later. At this point, the only potential cure for John was to receive a bone marrow transplant. His sister—let’s call her Mary—was a perfect match, and was willing to be a donor.

Since we had already found that John carried an inherited genetic alteration that likely contributed to his cancer, we tested to see if Mary carried the same mutation—unfortunately, she did.

The intention of a bone marrow transplant is to replace diseased stem cells (which make blood cells) with healthy stem cells from a donor. Since Mary carried the same genetic alteration as John, a transplant from her would have given John back the same genetic change that caused his cancer in the first place. Additionally, the process of donating her bone marrow may also have further increased Mary’s own risk of developing cancer. 

Outside of our clinic, this kind of testing is not done on a routine basis. This means that the inherited genetic alteration carried by both John and Mary would not have been identified, and the bone marrow transplant would have gone ahead—putting both of them at higher risk. This would have been a catastrophic situation, and one that was easily avoided using relatively simple genetic testing. Additionally, finding Mary’s genetic alteration allowed her to be enrolled into a screening and surveillance program through my clinic, which means that, if she does also develop cancer, we’ll catch it earlier.

Unlocking the power of the Gold Cohort

I strongly believe we need to bring this kind of genetic-informed care to cancer patients and their families everywhere in Canada, as John’s example so powerfully demonstrates. Encouragingly, the Marathon of Hope Cancer Centres Network provides an important opportunity to increase research in this area and to translate new knowledge into better care for patients.

Here in the Atlantic provinces, we’ve observed unusual clusters of two specific types of blood cancer: multiple myeloma and Waldenström’s macroglobulinemia. With Marathon of Hope Cancer Centres Network funding, we’ve been able to sequence the genomes of patients with these types of cancers across the Maritimes, allowing us to explore both environmental and genetic factors that increase the risk of these cancers.

So far in this project, we’ve already identified 12 patients with previously unknown inherited genetic mutations that likely contributed to their cancer. We’re currently validating these findings, but we expect to continue identifying more of these genetic variants as the project continues. This has important implications not only for these patients, but also for their family members, who can now get tested themselves to see if they’re also at higher risk of developing cancer and might benefit from increased screening.

Ours is only one of many projects contributing data to the Network’s Gold Cohort dataset—a critical resource that is providing researchers like me with valuable data to better study the hereditary aspects of different cancers. Crucially, the Gold Cohort includes comprehensive whole-genome profiling of participants’ tumour cells as well as their ‘normal’ non-cancerous cells. This is a treasure trove of information that allows us to investigate the complete genetic profile of people with cancer—so far, almost 16,000 of them treated across Canada.

The number and diversity of participants in the Gold Cohort, which includes a range of demographics as well as cancer types, means that we can now look for genetic alterations associated with cancer risk at a much larger scale than ever before. Cancer risk (or ‘predisposition’) genes tend not to be specific to one cancer type; whereas most studies to date focus on specific cancer types, this new dataset from a broad range of cancers will undoubtedly help us identify new patterns.

Importantly, the united national approach made possible by the Network also means that we can pool expertise and knowledge across the country. Hereditary cancer screening is still an emerging field—finding a new genetic alteration is one thing, but without proper interpretation it’s impossible to act on this finding. We have incredible expertise and knowledge in this country, and only by working together can we leverage that for the benefit of all cancer patients and their families, regardless of who they are or where they live.

I’ve seen remarkable progress in the field of hereditary cancer research already over the course of my career. Through the Marathon of Hope Cancer Centres Network, I’m confident that we can further accelerate our understanding of hereditary cancers and promote a more equitable and informed approach to identifying and addressing hereditary cancer risks.