Two new studies have found that large structural abnormalities in chromosomes, some of which have been associated with increased risk of cancer, can be detected in a small fraction of people without a prior history of cancer. The studies found that these alterations in chromosomes appear to increase with age, particularly after the age of 50, and may be associated with an increased risk for cancer. These studies were conducted by two consortia, one led by scientists at the National Cancer Institute (NCI), and one by Gene Environment Association Studies (GENEVA) which is sponsored by the National Human Genome Research Institute (NHGRI). NCI and NHGRI are both parts of the National Institutes of Health. The results of the studies were published online May 6, 2012, in Nature Genetics. Mosaicism, the type of structural abnormality in chromosomes that is described in these studies, results from a DNA alteration that is present in some of the body's cells but not in others. A person with mosaicism has a mixture of normal and mutated cells.
“These two studies provide large population-based evidence that genetic mosaicism increases with age and could be a risk factor for cancer. This last point raises an important issue with respect to the stability of a person's genome and suggests that detection of genetic mosaicism could be an early marker for detecting cancer, or perhaps other chronic diseases,” said Stephen Chanock, M.D., co-author and chief, Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, NCI. Scientists began observing an unexpected frequency of structural abnormalities in chromosomes during quality control checks of data from genome-wide association studies (GWAS) conducted in the GENEVA consortium and similar programs at NCI. These studies involve comparing hundreds of thousands of common differences across individual patients’ DNA to see if any of those variants are associated with a known trait, such as cancer. At first, these abnormalities were thought to be errors or outcomes of laboratory procedures. But they were found consistently at a low frequency, so the scientists wondered with what frequency these structural abnormalities occurred in the general population.