The accumulation of age-associated changes in a biochemical process that helps control genes may be responsible for some of the increased risk of cancer seen in older people, according to a National Institutes of Health study.
Scientists have known for years that age is a leading risk
factor for the development of many types of cancer, but why aging increases
cancer risk remains unclear. Researchers suspect that DNA methylation, or the
binding of chemical tags, called methyl groups, onto DNA, may be involved.
Methyl groups activate or silence genes, by affecting interactions between DNA
and the cell's protein-making machinery.
Zongli Xu, Ph.D., and Jack Taylor, M.D., Ph.D., researchers
from the National Institute of Environmental Health Sciences (NIEHS), part of
NIH, identified DNA methylation sites across the human genome that changed with
age. They demonstrated that a subset of those sites - the ones that become increasingly
methylated with advancing age - are also disproportionately methylated in a
variety of human cancers. Their findings were published online in the journal
Carcinogenesis.
"You can think of methylation as dust settling on an
unused switch, which then prevents the cell from turning on certain
genes," Taylor said. "If a cell can no longer turn on critical
developmental programs, it might be easier for it to become a cancer
cell."
Xu and Taylor made the discovery using blood samples from
participants in the Sister Study, a nationwide research effort to find the
environmental and genetic causes of breast cancer and other diseases. More than
50,000 sisters of women who have had breast cancer are participating in the
study.
The researchers analyzed blood samples from 1,000 women,
using a microarray that contained 27,000 specific methylation sites. Nearly
one-third of the sites showed increased DNA methylation in association with
age. They then looked at three additional data sets from smaller studies that
used the same microarray and found 749 methylation sites that behaved
consistently across all four data sets. As an additional check, they consulted
methylation data from normal tissues and seven different types of cancerous
tumors in The The Cancer Genome Atlas, a database funded by the National Cancer
Institute and the National Human Genome Research Institute.
Taylor said that DNA methylation appears to be part of the
normal aging process and occurs in genes involved in cell development. Cancer
cells often have altered DNA methylation, but the researchers were surprised to
find that 70-90 percent of the sites associated with age showed significantly
increased methylation in all seven cancer types. Taylor suggests that
age-related methylation may disable the expression of certain genes, making it
easier for cells to transition to cancer.
The research also determined how fast these methylation
events accumulate in cells. They occur at a rate of one per year, according to
Xu.
"On your 50th birthday, you would have 50 of these
sites [from the subset of 749] that have acquired methyl groups in each
cell," Xu said. "The longer you live, the more methylation you will
have."
For future work, Xu and Taylor want to examine more samples,
using a newer microarray that will explore methylation at 450,000 genomic
methylation sites. The additional samples and larger microarray, which will
provide 16 times more genomic coverage, will allow them to address whether
environmental exposures during adulthood or infancy affect methylation
profiles. These additional studies will help scientists better understand why
methylation happens as people march toward their retirement years.
DNA methylation is one of several epigenetic mechanisms that
can control gene expression without changes in DNA sequence. This study is part
of a broader research effort, funded by NIEHS, to understand how environmental
and other factors affect epigenetic mechanisms in relation to health.
To view in original source http://www.medicalnewstoday.com/releases/272187.php
Posts
No comments:
Post a Comment