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Evidence suggests cancer is not as solely genetic as previously believed

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According to a research review conducted by a leading expert at the University of Alberta, while cancer is a genetic disease, the genetic component is only one piece of the puzzle, and researchers must also consider environmental and metabolic factors.

According to David Wishart, professor in the departments of biological sciences and computing science, nearly all theories about the causes of cancer that have emerged over the last several centuries can be classified into three major groups. The first is cancer as a genetic disease, with an emphasis on the genome, or the set of genetic instructions that you are born with. The second is cancer as an environmental disease, with a focus on the exposome, which includes everything your body is exposed to throughout its lifetime. The third is cancer as a metabolic disease, with a focus on the metabolome, which includes all of the chemical byproducts of the metabolic process.

Until now, there hasn’t been much research into the metabolic perspective, but it’s piqued the interest of more scientists, who are beginning to understand the metabolome’s role in cancer.

As cancer develops and spreads, the genome, exposome, and metabolome interact in a feedback loop.

According to the data, heritable cancers account for only 5 to 10% of all cancers, according to Wishart. The remaining 90 to 95 percent are caused by exposome factors, which in turn cause genetic mutations.

"That's an important thing to consider, because it says that cancer isn't inevitable."

The metabolome is critical to the process because the cancer-specific metabolome sustains the genetically mutated cancer cells.

"Cancer is genetic, but often the mutation itself isn't enough," said Wishart. 

Cancer creates its own environment and introduces specific metabolites as it develops and spreads in the body.

"It becomes a self-fuelled disease. And that's where cancer as a metabolic disorder becomes really important."

When thinking about cancer, the multi-omics perspective, in which the genome, exposome, and metabolome are all considered simultaneously, is showing promise for finding treatments and overcoming the limitations of looking at only one of these factors.

Researchers who focus solely on the genetic perspective, for example, are looking to address specific mutations, according to Wishart. The problem is that there are approximately 1,000 genes that can become cancerous when mutated, and cancer typically requires at least two different mutations within these cells to grow. That means there are a million potential mutation pairs, and narrowing down the possibilities when looking for new treatments “becomes hopeless.”

However, when it comes to cancer metabolism, there are only four major metabolic types, according to Wishart. Rather than attempting to find a treatment plan for a single mutation combination among a million, determining the patient’s cancer metabolic type can immediately guide doctors in deciding on the best treatment for their specific cancer.

"It really doesn't make a difference where the cancer is -- it's something you've got to get rid of. It's how it thrives or grows that matters," said Wishart. "It becomes a question of, 'What's the fuel that powers this engine?'"

Wishart cautioned that health-care providers still require a combination of cancer therapies, and that a better understanding of the metabolome and its role in the cancer feedback loop is also critical to cancer prevention.

"If we understand the causes of cancer, then we can start highlighting the known causes, the lifestyle issues that introduce or increase our risk," he said.
"From the prevention side, changing our metabolism through lifestyle adjustments will make a huge difference in the incidence of cancer."

Genome Canada, the Canadian Institutes of Health Research, and the Canada Foundation for Innovation funded the review of research.

STORY SOURCE:
Materials provided by University of Alberta. Original written by Adrianna MacPherson.

Note: Content may be edited for style and length.

JOURNAL REFERENCE:
David Wishart. Metabolomics and the Multi-Omics View of Cancer. Metabolites, 2022; 12 (2): 154 DOI: 10.3390/metabo12020154

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