Study identifies causes of cancer

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

They write in a new article, published in Molecular biology and evolutionthat their new molecular analysis approach brings clarity to a long-standing debate about the degree of control humans have over the development of cancer over time.

Examining cases 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., Elihu Professor of Biostatistics in the Department of Biostatistics at the ‘YSPH.

“We can now answer the question – to the best of our knowledge – ‘What is the underlying source of the key mutations that turned these cells into cancer instead of remaining normal tissue?’ “, did he declare.

Some of the most prevalent cancers in the United States are known to be highly preventable by human decisions. Skin cancers like melanoma are largely caused by prolonged exposure to ultraviolet light, and lung cancers can often be attributed to tobacco use. But scientists have long struggled to gauge the extent to which an individual’s tumor has grown as a result of preventable actions versus aging or “luck”.

Previously, scientists have shown they can reliably predict how certain factors cause specific genome-altering mutations in tissues. 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 fault to be attributed to known and unknown but identified factors in the emergence of cancer.

“It gives us the final piece of the puzzle to connect what happened to your genome with cancer,” he explained. “It’s really direct: we look at your tumor and we see the signal written in your tumor of what caused this cancer.”

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

For example, preventable factors account for much of the formation of bladder and skin tumors. However, they found that prostate cancers and gliomas are largely attributable to age-related internal processes.

Local populations or professions that suffer from abnormally high levels of cancer may also be able to use the results for cases of exposure to carcinogens, Townsend suggested. The idea seems promising, he said, because capturing the proportion of factors could potentially expose the underlying causes that led to tumor growth.

“It can be useful for giving people feedback that lets them know what caused their cancer,” he said. “Not everyone may want to know. But on a personal level, it can be helpful for people to attribute their cancer to its cause.”

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

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

“A public health intervention aimed at minimizing exposure to these avoidable signatures would attenuate disease incision by preventing the accumulation of mutations that directly contribute to the cancer phenotype,” the researchers wrote in the study.

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

Provided by Yale School of Public Health