One of the textbook explanations for why some people are at higher risk for cancer is a lifestyle, or alternatively ‘bad habits’. We often hear that smoking increases our risk of developing lung cancer or that a high-fat diet increases our risk of developing bowel cancer, but not all people. smokers get lung cancer and not everyone who eats cheeseburgers gets bowel cancer. ‘Other factors’ have to play.
Now, new research from Calgary University scientist Dr Edwin Wang, PhD, sheds light on these ‘other factors’. Wang has found seven fingerprints or DNA patterns that explain the risk of cancer. The research is published in Advances in science.
This finding rewrites the textbook’s explanation that cancer occurs due to human behavior along with a few bad luck to include a person’s genetic make-up. We believe that a baby is born with and does not change a germline genomic pattern, and that pattern is associated with a lower or higher risk of cancer. “
Dr. Edwin Wang, Ph.D., Scientist, University of Calgary
The research offers a new perspective on the risk of multi-generational disease as the germline represents the cells that make up our children and the DNA that is passed from parent to child. This is the first time that scientists have described these highly specialized biological patterns associated with cancer risk.
Wang, a cancer systems biologist and big data scientist, holds the Alberta Innovates Translation Chair in Cancer Genomics. It assumes that everyone’s response to these risk categories makes them highly susceptible to cancer, similar to a sliding scale. A member of the Alberta Children’s Hospital Research Institute (ACHRI) and the Arnie Charbonneau Cancer Institute at the School of Cumming Medicine, Wang found that DNA fingerprints could be categorized into subgroups with specific survival rates. One of the seven germlines offers protection from developing cancer, while the other six germlines are at increased risk for cancer.
“Interestingly, one of these germlines is immune to the development of cancer and has appeared frequently in our analysis of genomes,” says Wang, a professor in the CSM’s Department of Biochemistry and Molecular Biology. . “We know there are individuals who can smoke and have an unhealthy lifestyle but never get cancer, and this discovery may explain those onions.”
For this research, Wang systematically analyzed more than 26,000 germline genomes of individuals, approximately 10,000 people with cancer, and the rest without. His team analyzed computer files from cancer patients at the National Cancer Institute – data collected by the National Institutes of Health for the Atlas Genome Atlas, part of the National Institutes of Health in the U.S. The samples are included 22 specific cancers, including lung, pancreatic, bladder, chest, brain, stomach, thyroid, and bone and a dozen more. The control group of non-cancer people included genomic groups from Sweden, England and Canada.
The vast amount of data could only be processed by machine learning. Wang’s lab is equipped to handle data through superfast networks at UCalgary. This research requires a large amount of computer storage: 10 million terabytes. To help understand this volume, one terabyte can store 250 films.
“Even at high speeds, with two streams running 24/7, it took three months straight to our lab just to download the biological information containing billions and billions of nucleotides in each genome individually, “Wang said.
Wang notes that between five to 10 percent of cancers are caused by specific gene mutations. Think of breast cancer and the inherited gene BRCA1 and BRCA2, a much-modified gene mutation by actress Angelina Jolie. Wang has always suspected that these inherited cancers represent only a handful of associations and studied in-depth with advanced genomic capabilities to achieve more connections.
“We wanted to investigate whether a genomic pattern or sequential imaging that occurs frequently in genomes could be a promising measure for genetic prediction of cancer,” Wang said.
“We found that single DNA fingerprints were enriched tens to hundreds of times in germline genomes of cancer patients, suggesting that it is a universal hereditary property encoding cancer risk.” the research also found that other DNA fingerprints were significantly enriched in cancer patients who also smoked tobacco, indicating a higher risk in smokers who have such DNA fingerprints.
Genomic medicine diagnoses disease more efficiently, more cost-effectively, and can help people make health decisions throughout their lives. Wang’s research lays the foundation for tools that can help cancer specialists and family physicians to guide patients. “I hope that more studies will be carried out to expand this work, so that it is eventually implemented allowing clinicians to inform patients about their cancer risk and how take steps to ensure a healthy life. “
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Magazine Reference:
Xu, X., et al. (2020) Germline genomic patterns are associated with cancer risk, oncogenic pathways, and clinical outcomes. Advances in science. doi.org/10.1126/sciadv.aba4905.