Lifestyle, or in other words ‘bad habits’, is one of the textbook explanations for why some people are at higher risk of cancer. We often hear that smoking increases the risk of developing lung cancer or that a high-fat diet increases the risk of bowel cancer, but not all smokers get lung cancer and not all people who eat cheeseburgers get bowel cancer. ‘Other factors’ must be at play.
Now a new study by a University of Calgary scientist, Dr. Edwin Wang, sheds light on these “other factors”. Wang discovered seven DNA fingerprints or patterns that define cancer risk. The research was published in Scientific progress.
This finding transcribes the explanation from the textbook that cancer occurs due to human behavior combined with bad luck, including genetic composition. We believe that a child is born with a genomic germ pattern and this will not change, and this pattern is associated with a greater or lesser risk of cancer. “
Dr. Edwin Wang, scientist, University of Calgary
The research offers a new insight into the risk of multiple generations because the germ represents the cells that determine our children and the DNA that is passed from parents to children. This is the first time that scientists have described these highly specialized biological patterns applicable to cancer risk.
Wang, a cancer system biologist and big data scientist, holds the Alberta Innovates Translational Chair in Cancer Genomics. It assumes that they all fit into these risk categories which makes them more or less predisposed 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 Cumming Medical School, Wang found that DNA fingerprints can be classified into subgroups with different survival rates. One in seven germs offers protection against the development of cancer, and the other six germs pose a higher risk of cancer.
“Interestingly, one of these germs protects against cancer development and has frequently appeared in our genome analysis,” says Wang, a professor in the Department of Biochemistry and Molecular Biology at CSM. “We know that there are individuals who can smoke and have an unhealthy lifestyle, but they never get cancer, and this discovery may explain these phenomena.”
For this study, Wang conducted a mass systematic analysis of more than 26,000 germ genomes, about 10,000 people who had cancer and were left without. His team analyzed computer files of cancer patients at the National Cancer Institute – data collected by the National Institutes of Health for the Cancer Genome Atlas, part of the National Institutes of Health in the United States. Samples include 22 different cancers, including lung, pancreas, bladder, breast, brain, stomach, thyroid and bone, and a dozen more. The control group of cancer-free people included genomically sequenced groups from Sweden, England, and Canada.
Huge amounts of data could only be processed with machine learning. Wang’s lab is equipped to process data via ultra-fast networks in UCalgary. This research requires a huge amount of computer memory: 10 million terabytes. To help you understand this amount of sound, you can store 250 movies on one terabyte.
“Even at high speeds, with two streams working 24 hours a day, seven days a week, it took us labs three months in a row to retrieve biological information containing billions and billions of nucleotides in each individual genome,” Wang says.
Wang notes that between five to 10 percent of cancers are caused by certain gene mutations. Imagine breast cancer and the inherited gene BRCA1 and BRCA2, a mutation in a gene that actress Angelina Jolie was widely known for. Wang always suspected that these hereditary cancers represented only a few associations and undertook a deeper investigation with advanced genomic abilities to give more associations.
“We wanted to investigate whether a genomic pattern or a significant, sequential profile that often appears in genes can serve as a promising measure of genetic predisposition to cancer,” Wang says.
“We found that one DNA fingerprint is enriched tens to hundreds of times in the genomes of germline patients with cancer, suggesting that it is a universal inherited trait that encodes cancer risk.” The study also found that another DNA fingerprint was highly enriched in cancer patients who were also tobacco smokers, indicating that smokers who carry such a DNA fingerprint have a higher risk of cancer.
Genomic medicine makes the diagnosis of the disease more efficient, cost-effective and can help people make health decisions throughout their lives. Wang’s research lays the groundwork for tools that could help cancer experts and family physicians guide patients. “I hope that additional studies will be conducted to expand this work, so that it can eventually be put into practice by allowing clinicians to inform patients about the risk of cancer and how to take precautions to ensure a healthy life.”
Xu, X., and others. (2020) Genomic germ patterns are associated with cancer risk, oncogenic pathways, and clinical outcomes. Scientific progress. doi.org/10.1126/sciadv.aba4905.