February 4, 2014
Reasons For Age-Related Cancer Incidence Increase Identified
redOrbit Staff & Wire Reports - Your Universe Online
Age-related changes in a biochemical process known as DNA methylation could be responsible for the increased risk of cancer in older men and women, according to research appearing in the latest edition of the journal Carcinogenesis.
While medical experts have long known that the aging process is a leading risk factor for the development of several different types of cancer, the exact reasons for that phenomenon have remained unclear. However, many experts have long suspected that DNA methylation might be involved.
As the researchers explained in a statement Monday, DNA methylation is a process during which chemical tags known as methyl groups bind themselves onto genetic material. Methyl groups activate or silence genes by influencing the interactions between DNA and the protein-making mechanisms of cells.
“You can think of methylation as dust settling on an unused switch, which then prevents the cell from turning on certain genes,” study author Dr. Jack Taylor of the National Institute of Environmental Health Sciences (NIEHS) said in a statement. “If a cell can no longer turn on critical developmental programs, it might be easier for it to become a cancer cell.”
As part of their research, Dr. Taylor and his NIEHS colleague Dr. Zongli Xu conducted a genome-wide analysis in search of age-related DNA methylation sites that changed with age, then examined their relationships to cancer and other underlying epigenetic marks. They found that one subset of those sites that become increasingly methylated with age are also disproportionately methylated in multiple types of human cancers.
Using blood samples obtained from more than 1,000 35- to 76-year-old women participating in the Sister Study (a national research initiative to detect the environmental and genetic causes of breast cancer and similar diseases), they focused their efforts on a microarray of 27,000 specific methylation sites.
Dr. Taylor and Dr. Xu found age-related increases in DNA methylation in nearly one-third of those sites, the NIEHS explained in a statement. Next, they looked at three additional data sets from similar research using the same microarray, and located 749 methylation sites that behaved consistently across all four data sets.
“Based on The Cancer Genome Atlas data, we show that these age-related changes are largely concordant in a broad variety of normal tissues and that a significantly higher... that expected proportion” of increasingly methylated age-related sites in several different types of tumors, the authors wrote.
Genes containing those areas were found to be “highly enriched for developmental and signaling pathways,” they added. “Our findings suggest that as cells acquire methylation at age-related sites, they have a lower threshold for malignant transformation that may explain in part the increase in cancer incidence with age.”