Genetic discovery may lead to new blood test for people at high risk for cancer

Research funded in part by the Canadian Cancer Society may lead to a genetic screening test that could help families who are at high risk for cancer.

Researchers have found that a recently discovered genetic occurrence, called 'DNA copy number variation' (CNV), may be linked to an increased risk of cancer in people with Li-Fraumeni syndrome (LFS), a hereditary disease that already increases their susceptibility to cancer.

CNV refers to the variation in the number of copies (normally two) of a gene or sequences of DNA in the genome of an individual. The variations have been associated with susceptibility to certain diseases. This is the first genome-wide study to look at CNVs and genetic susceptibility to cancer.

Because the study also found that CNVs can be detected in the blood, the discovery paves the way for the development of a blood test to detect those people with LFS at greatest risk of developing cancer.

"One of the challenges of caring for patients with Li-Fraumeni syndrome is that it is difficult to predict when a cancer may develop," says lead researcher Dr. David Malkin, a pediatric oncologist and senior scientist at The Hospital for Sick Children. "These findings suggest that screening for CNVs in families predisposed to cancer may help identify those who are at highest risk and help us to detect any cancer early."

Heather Chappell, senior manager of Cancer Control Policy for the Canadian Cancer Society says, "Early detection is critical because we know that most cancers can be treated if they are caught early enough. This is important research that is bringing us closer to answers and options for people with Li-Fraumeni syndrome."

LFS is a rare hereditary condition that increases the risk of children and young adults developing, most commonly, breast, brain, bone and soft tissue tumours. However, the disease can be unpredictable. Different individuals within a single family can develop tumours of varying severity, at different body sites and at different ages.

Using the latest technology, the research team analyzed the DNA of healthy individuals and families affected by LFS. The team found significantly more CNVs present in LFS study subjects than in healthy subjects. They found more CNVs in LFS patients who had already developed cancer and more CNVs in the children of LFS parents. And perhaps most importantly, they found the greatest number of CNVs present in Li-Fraumeni patients who had already developed cancer compared to those who had not yet developed the disease. This finding suggests a strong link between CNV frequency and the severity of the cancers they develop. The researchers say the next step is to investigate the link between CNVs and tumour development and progression, and to determine whether similar findings are evident in other populations of cancer patients.

The Canadian Cancer Society has been a leader in research into Li-Fraumeni syndrome, providing more than $2 million to Dr. Malkin since 1995 for his studies in this field.

This study is being published in the Aug. 5, 2008 issue of the Proceedings of the National Academy of Sciences.

A survivor's story

Luana Locke isn't afraid to face her genetic destiny square in the eyes. Li-Fraumeni syndrome runs in Ms. Locke's family, which has been devastated by cancer. In fact, she is the only member of her family who has had cancer and survived. She was diagnosed with breast cancer at the age of 25. Her children have also inherited the condition.

"As a cancer survivor and mother of two kids who will likely face a cancer diagnosis in the near future, I'm happy that I've equipped myself through genetic testing and screening with the best possible tools to deal with all possible outcomes," says Ms. Locke.

It's been a difficult series of uphill battles since the diagnosis, Ms. Locke admits. Most recently, her nephew passed away on his fifth birthday earlier this year. However, she said that the "power of knowledge" has made all the difference in the early detection of her syndrome and further research means even more hope for her children.

"Whatever road LFS takes me down, I still celebrate that I'll never have to lie awake at night and ask myself those questions as a parent. I'm doing whatever I can to prevent my kids from being victimized by this disease. The questions you ask, the answers you seek give me and others like me hope - hope that the legacy of loss will, in the very near future, end."