and Medicine for Seniors
Many Elderly Found with Puzzling Mutations Linked to
Researchers find no connection with blood cancer that
seldom strikes senior citizens
Oct. 22, 2014 A surprisingly large percentage 5
percent of senior citizens over age 70 have been found to have genetic
mutations linked to leukemia and lymphoma in their blood cells. The vast
majority won't get blood cancer, however, as the incidence of these
cancers is less than 0.1 percent among the elderly, according to the
researchers at Washington University School of Medicine in St. Louis.
Mutations in the body's cells randomly accumulate
as part of the aging process, and most are harmless. For some people,
genetic changes in blood cells can develop in genes that play roles in
initiating leukemia and lymphoma even though such people don't have the
blood cancers, the scientists reported Oct. 19 in Nature Medicine.
"But it's quite striking how many people over age
70 have these mutations," said senior author Li Ding, PhD, of The Genome
Institute at Washington University. "The power of this study lies in the
large number of people we screened. We don't yet know whether having one
of these mutations causes a higher than normal risk of developing blood
cancers. More research would be required to better understand that
The researchers analyzed blood samples from 3,000
people enrolled in The Cancer Genome Atlas project, a massive endeavor
funded by the National Cancer Institute and the National Human Genome
Research Institute at the National Institutes of Health (NIH). The
effort involves cataloguing the genetic errors involved in more than 20
types of cancers.
The patients whose blood was analyzed for the
current study had been diagnosed with cancer but were not known to have
leukemia, lymphoma or a blood disease.
They ranged in age from 10 to 90 at the time of
diagnosis and had donated blood and tumor samples before starting cancer
treatment. Therefore, any mutations identified by the researchers would
not have been associated with chemotherapy or radiation therapy, which
can damage cells' DNA.
The researchers, including Genome Institute
scientists Mingchao Xie, Charles Lu, PhD, and Jiayin Wang, PhD, zeroed
in on mutations that were present in the blood but not in tumor samples
from the same patients. Such genetic changes in the blood would be
associated with changes in stem cells that develop into blood cells, but
not to the same patient's cancer.
They looked closely at 556 known cancer genes. In
341 patients ages 40-49, fewer than 1 percent had mutations in 19
leukemia- or lymphoma-related genes. But among 475 people ages 70-79,
over 5 percent did. And over 6 percent of the 132 people ages 80-89 had
mutations in these genes.
The researchers noted that nine of the 19 genes
were mutated repeatedly, an indicator that the changes drive or initiate
the expansion of blood cells with these mutations.
This expansion of cells is clearly not leukemia or
lymphoma, the researchers said. It may be a precursor to blood cancers
in a small subset of patients, but the study was not designed to predict
the future risk of developing these diseases.
The current study likely underestimates the
percentage of people with mutations in leukemia and lymphoma genes
because the researchers only were able to identify small mutations, not
large structural variations or the insertions and deletions of chunks of
Still, it would be premature for people to undergo
genetic testing to see if they have mutations linked to leukemia and
lymphoma as a means to predict their risk of blood cancers.
"We would not want anyone to think they should be
screened for these mutations to understand their risk of leukemia or
lymphoma," said co-author and leukemia scientist Timothy Ley, MD, the
Lewis T. and Rosalind B. Apple Professor of Oncology. "The ability to
understand how mutations in these genes increase a person's risk of
blood cancers is a long way off, and genetic testing would be of no
benefit at this time."
If the researchers repeated the study in tens of
thousands of patients and tracked the development of mutations over
time, they could more accurately identify the risk of individual
mutations or combinations of mutations for the development of leukemia
and lymphoma. Such a study is intriguing to contemplate but would take
years to complete and require considerable financial resources, Ding
The research was funded by the National Cancer
Institute and the National Human Genome Research Institute at the
National Institutes of Health (NIH).