Yale Research Identifies Causes of Cancer

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By Yale School of Public Health May 12, 2022

A team of researchers led by Yale University scientists can now quantify the factors causing changes in the DNA that contribute most to cancer growth in tumors of most major tumor types.

In a new paper published in the journal Molecular Biology and Evolution, they say that their new molecular analysis approach clarifies a long-standing debate about how much control humans have over cancer development over time.

Looking at the instances of specific genetic mutations can reveal the extent to which preventable exposures like ultraviolet light caused tumor growth in 24 cancers, said Jeffrey Townsend, Ph.D., the Elihu Professor of Biostatistics in the Department of Biostatistics at Yale School of Public Health (YSPH).

“We can now answer the question — to the best of our knowledge — ‘What is the underlying source of the key mutations that changed those cells to become a cancer instead of remaining normal tissue?’” he said.

Some of the most common cancers in the United States are known to be highly preventable by human decisions. Skin cancers, such as melanoma, emerge in large part because of prolonged exposure to ultraviolet light, and lung cancers can often be traced back to tobacco use. But scientists have long struggled to gauge how much any individual’s tumor developed as a result of preventable actions versus aging or “chance.”

Previously, scientists have demonstrated that they can reliably predict how certain factors that cause specific mutations that alter the genome in tissues. By combining this knowledge with their method that quantifies the contribution of each mutation to cancer, Townsend and his colleagues showed the specific percentage of the blame to be assigned to known and unknown but identified factors in the emergence of cancer.

“That gives us the last puzzle piece to connect what happened to your genome with cancer,” he explained. “This is really direct: We look in your tumor, and we see the signal written in your tumor of what caused that cancer.”

They write in their report that some cancers are more controllable than others.

“We can now answer the question — to the best of our knowledge — ‘What is the underlying source of the key mutations that changed those cells to become a cancer instead of remaining normal tissue?’”

— Jeffrey Townsend, Ph.D., Elihu Professor of Biostatistics and Professor of Ecology and Evolutionary Biology


Not all genetic changes that lead to tumors are incorporated into the current approach, so that more research is needed to fully understand complex genetic changes like duplicated genes or chromosomes. Scientists continue to discover new factors that also lead to tumor growth, so Townsend cautioned that it current approaches do not provide a “complete accounting.” And his team’s method remains untried on many less-frequent cancers that the group has not yet studied.

Still, the findings could help public health officials to quickly recognize sources of cancer before they lead to more tumors, thereby saving lives.

“Public health intervention targeted at minimizing exposure to these preventable signatures would mitigate disease severity by preventing the accumulation of mutations that directly contribute to the cancer phenotype,” the researchers wrote in the study.

Reference: “Attribution of cancer origins to endogenous, exogenous, and preventable mutational processes” by Vincent L. Cannataro, Jeffrey D. Mandell and Jeffrey P. Townsend, 26 April 2022, Molecular Biology and Evolution.
DOI: 10.1093/molbev/msac084

Co-researcher Jeffrey Mandell works at the Yale Department of Computational and Biology Informatics as a Ph.D. student. Vincent Cannataro, the study’s first author, is an assistant professor of biology at Emmanuel College.

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https://scitechdaily.com/yale-research-identifies-causes-of-cancer/

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