Cancer patients to be offered genomic testing as part of a joint study with U.S. hospitals

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Over the next five years, every patient treated at Canada’s largest cancer centre will have the opportunity to undergo genomic testing to see if major hereditary health risks lurk in their DNA.

The Princess Margaret Cancer Centre in Toronto announced Thursday that it would become the first Canadian hospital to join a cross-border collaboration involving 15 hospitals in the United States and Helix, Inc., a private American genomics company, that together plan to sequence the exomes of 1.6 million patients.

Whole exome sequencing analyzes the protein-coding regions of all 25,000 genes. Although the exome contains less than 2 per cent of the human genome, it contains most of the mutations known to pass diseases down through families.

Sequencing of so many people could unlock new discoveries about the genetic roots of disease, while at the same time providing patients with information about their own risk of developing certain cancers or an inherited type of high cholesterol, according to Raymond Kim, Medical Director of Cancer Early Detection and the Bhalwani Familial Cancer Clinic at Princess Margaret.

“It’s not just a research study that is for science,” he said. “It has direct relevance for patients.”

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Dr. Kim is the principal investigator for the Princess Margaret study, called OurGenes. It aims to enroll 100,000 Princess Margaret patients, which Dr. Kim said makes it “one of the largest, if not the largest,” study of its kind in Canada. It is expected to start immediately.

The 15 American hospitals that have already joined the Helix Research Network have each committed to enrolling 100,000 patients. It’s expected that a number of studies will come out of the work.

Patients won’t receive information about every remote genetic risk uncovered during screening, Dr. Kim explained. Instead, they will be informed if they carry genetic mutations that predispose them to three syndromes, which were chosen because the U.S. Centers for Disease Control and Prevention believed screening for them has the highest likelihood of benefiting public health.

The conditions are: hereditary breast and ovarian cancer owing to mutations on the BRCA1 or BRCA2 genes; Lynch syndrome, which raises the risk of colorectal and endometrial cancer; and familial hypercholesterolemia, or FH.

FH, which is caused by mutations in a small subset of genes, is linked to high cholesterol. The syndrome leads to a 20-fold increase in early-onset heart disease if not caught early and treated with preventative medications, said Ari Morgenthau, an endocrinologist at University Health Network, a group of Toronto hospitals that includes Princess Margaret.

Dr. Morgenthau is overseeing the FH portion of the OurGenes study.

“There’s been a lot of effort to improve our recognition of it,” Dr. Morgenthau said of FH, “and this will be a great opportunity to see how we can further advance.”

At first blush, it may seem too late for cancer patients to benefit directly from genomic testing and the cancer-prevention strategies it can trigger, such as more frequent colonoscopies and mammograms or prophylactic mastectomies.

After all, they’re already sick. But Dr. Kim explained it this way: Imagine you’ve been diagnosed with cervical cancer, a disease that is almost always caused by the sexually transmitted human papillomavirus, or HPV.

Exome sequencing could reveal you also have a BRCA1 mutation or familial hypercholesterolemia.

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Laura Redondo, a genetic counsellor at Princess Margaret and the clinical lead for the study, said discovering one of these inherited syndromes in a patient would open the door for genetic testing of relatives who may be susceptible to the same inherited diseases.

“That’s really the power of genetic testing,” Ms. Redondo said. “It’s that carrier testing or cascade testing, where we can detect cancer early and save lives.”

Dr. Kim said offering whole exome sequencing to as many as 100,000 patients over five years is expected to cost about $20-million, including the USD$100 cost of each screening test. The bill is being footed by the cancer centre’s philanthropic foundation.

Participation is free and voluntary.

Princess Margaret had hoped to launch OurGenes earlier in the year, but the centre ran into delays arising from the chilly relations between Canada and the U.S. since President Donald Trump took office for a second time.

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Dr. Kim said the Princess Margaret research ethics board took about six months longer than expected to approve the study because board members wanted to be doubly certain that patients’ health information would be protected after their blood samples were sent to a San Diego sequencing lab run by Helix.

“Our research ethics board had concerns about samples going to the U.S., and we had to work very hard to figure out the privacy to ensure that Canadians – who don’t even want to visit the U.S. – are comfortable with the safeguards for their genetic material to go to the U.S.,” Dr. Kim explained.

Information sent to Helix will be stripped of details that could identify patients.

Only the Princess Margaret team will be able to marry exome sequencing results with patient files in a way that can identify them, said Larissa Peck, a genetic counsellor at Princess Margaret and project lead.

Participants who learn they have a worrisome mutation will then be offered genetic counselling to help them reduce their risk of cancer or FH.