July 9, 2007
TheStar.com

Ontario-led Study Finds Cancer Marker

BY Megan Ogilvie

Discovery paves way for new colorectal test to prevent disease that kills 5,000 annually

An Ontario-led team of international scientists has helped find the first genetic predictor for colorectal cancer, a discovery that heralds a new era of screening for the second deadliest form of cancer in the country.

The finding could lead to a test for the thousands of Canadians who have family members with the disease, making it easier to predict their likelihood of getting colorectal cancer and, ultimately, helping to prevent it.

After sifting through more than 100,000 pieces of genetic material from 15,000 people, the Canadian team identified a specific site on Chromosome 8 associated with colorectal cancer. Research teams from Britain and the United States also found the same site on the same chromosome.

Having the site increases a person's risk of getting colorectal cancer by about 20 per cent, said Dr. Tom Hudson, president of the Ontario Institute for Cancer Research and co-leader of the study.

Previous studies have linked the same site to prostate cancer and to breast cancer, which means it could be responsible for a multitude of common cancers, he said.

Experts are calling the trio of studies from the three research teams, published yesterday in the journal Nature Genetics, a breakthrough for some 2,500 Canadians who will be affected by the familial form of the disease every year.

They say the new genetic information will help identify people at risk for the disease and could lead to new tests and prevention methods.

"This is the first example of our ability to look at somebody, even in childhood or in utero, and make predictions of their lifetime risk of colon cancer," said Dr. Brent Zanke, a scientist at Cancer Care Ontario and co-leader of the study, which used findings from the ongoing Assessment of Risk for Colorectal Tumours in Canada project.

Roughly 12,000 Canadians will get colorectal cancer this year and almost 5,000 will die from the disease. Ontario, which has one of the highest colorectal cancer rates in the world, will see an estimated 7,800 people diagnosed in 2007 and about 3,200 die.

But colorectal cancer is 90 per cent curable – if detected early enough, said Terry Sullivan, president and CEO of Cancer Care Ontario, the agency in charge of provincial cancer services.

Colorectal cancer can be detected either by a fecal blood test, which looks for small traces of blood that may indicate cancer, or by a colonoscopy.

Right now, people with a family history of colorectal cancer know they are at risk of getting the disease, but they don't know how high that risk might be, said Sullivan. The finding will help scientists devise a test to tell people their lifetime risk of colorectal cancer, as well as practical tools to advise them at what age and how often they should get screened, he said.

"We can focus prevention in a much more precise way for a relatively large number of people who have familial patterns of colorectal cancer. That's the importance of the breakthrough."

Using information gleaned from the International HapMap Project, a groundbreaking catalogue of genetic differences and similarities between people, the trio of research groups all found the genetic variant linked to colorectal cancer on Chromosome 8q24.

The Canadian team scanned the genomes of 7,480 people with colorectal cancer and 7,779 people without. Study participants came from Ontario, Seattle, Newfoundland, Scotland and France.

A region on chromosome 8q24, close to a single nucleotide polymorphism, or SNP, called rs6983267, emerged as a common genetic variant linked with colorectal cancer. SNPs are changes in the DNA sequence that occur when a single nucleotide – A, T, C or G – is altered during replication.

There are 10 million SNPs strewn throughout the genome and they help create an individual's unique DNA pattern. Scientists are just starting to figure out their possible role in disease.

Stephen Chanock, a senior scientist at the National Cancer Institute in Bethesda, Md., and a collaborator with the Canadian team, said chromosome 8q24 has been an important region in cancer research for almost 10 years. He said researchers hope to soon unravel why the region gets disrupted and increases cancer risk.

"We have in front of us the rich opportunity to go and look at one of the master regions linked to cancer," said Chanock, who earlier this year linked chromosome 8q24 to prostate cancer.

Hudson and his colleagues are planning to scan another 500,000 genetic markers over the next six months to look for more genetic predictors of colorectal cancer.

Zanke says the finding is an early example of how medicine is going to change in the wake of the human genome being assembled five years ago. He believes doctors will soon be able to give people a personalized health prescription based on their genetic makeup.

"It could be feasible to look inside someone's genes, the 1.5 billion pieces of genetic information, to find a profile that could predict their predisposition for colon cancer and other diseases."