Finding causes brings us closer to cures
By YALE SCHOOL OF PUBLIC HEALTH
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| Illustration of human cancer cells. |
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.
For example, preventable factors account for a large part of the formation of tumors of the bladder and skin. However, they found that prostate cancers and gliomas are largely attributable due to internal age-associated processes.
Local populations or professions who suffer from inordinately high
levels of cancer may also be able to use the findings to discover instances of
exposure to carcinogenic substances, Townsend suggested. The idea seems
promising, he said, because capturing the proportion of factors could
potentially expose the underlying causes which led to tumor growth.
“It can be useful in terms of giving people feedback that lets
them know what the causes of their cancer are,” he said. “Not everyone may wish
to know. But on a personal level, it may be helpful to people to attribute
their cancer to its cause.”
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.