Research Shows 1st Link Between Age, Cancer Risk : Medicine: A USC study proves a long-held belief in the scientific community that genetic mutations increase as people grow older, raising the potential for malignancy.
A USC researcher has provided the first direct evidence that cancer-causing mutations of genes accumulate with age, thereby raising the risk of cancer.
It is an article of faith for many researchers that these mutations, caused by a breakdown of the body’s normal repair mechanisms, are responsible for the high incidence of cancer among the elderly. But until now, there has been little experimental support for the idea.
Using new genetic engineering technology, however, molecular pharmacologist Gino Cortopassi of USC has studied the incidence of a specific mutation in a gene called BCL2, which plays a major role in the development of non-Hodgkin’s lymphoma, a cancer of the lymph nodes that strikes 45,000 Americans each year, killing about 21,000.
Cortopassi and his colleagues report today in the Proceedings of the National Academy of Sciences that the incidence of mutations is 40 times as high in spleen tissue from people over age 60 as it is in people under 20.
Significantly, the risk of developing lymphoma is also 40 times as high in people over age 60 as it is in people under 20.
In a separate study, Cortopassi has also found a two- to three-fold increase in the incidence of BCL2 mutations among smokers and a corresponding increase in the risk of non-Hodgkin’s lymphoma.
The finding provides new impetus for researchers who are trying to reduce the risk of cancer by finding ways to block the mutations, such as by the use of antioxidants like Vitamins C and E.
The study “may also provide valuable insights into the cause of non-Hodgkin’s lymphoma,” which has a yearly rate of increase exceeded only by lung cancer in women and melanoma in both men and women, according to Dr. Nathaniel Rothman of the National Cancer Institute. “It’s increasing and we don’t know why,” he said.
The incidence of non-Hodgkin’s lymphoma has increased by more than 65% since the early 1970s, according to the American Cancer Society. Part of the increase is a result of the above-normal incidence of lymphoma among AIDS patients, but the mysterious majority of it is apparently unrelated to that epidemic. “It’s an important public health issue,” Rothman said, “and this is an exciting finding.”
Researchers have long known that the incidence of cancer increases with age. While one of every 60 men under the age of 40 develop cancer, fully one of every three between the ages of 60 and 79 do so. For women, the corresponding figures are one of 52 and one of four.
Most researchers believe that this increase results from the slow but steady accumulation of genetic defects caused by exposure to chemicals in the environment, radiation and viruses. As it ages, the body loses the ability to repair those defects.
A handful of scientists have previously been able to demonstrate the accumulation of such defects in body cells, but those studies have focused on defects that play no role in cancer formation.
Cortopassi chose to look at BCL2 because it plays a clear role in triggering lymphoma and because it contains what researchers call a genetic “hot spot,” an area particularly prone to mutations. The gene controls a process called apoptosis, which directs cells to commit suicide after they have been damaged, genetically or otherwise.
When BCL2 itself is damaged, the cell survives while genetic defects accumulate. Over time, enough damage can accumulate to trigger cancer.
Cortopassi collected blood samples from 53 living people and from 31 autopsies conducted at Los Angeles County-USC Medical Center. Using a technology called polymerase chain reaction--the same PCR technology used to perform DNA fingerprinting in the O.J. Simpson case--he measured the number of genetic defects, called translocations, at the “hot spot” in both blood cells and spleen tissue.
He found 13 times as many translocations in blood cells from 60-year-olds as from 20-year-olds and 40 times as many in spleen tissues.
Cortopassi conceded that his results do not prove that the mutations cause cancer. That will require a second step in which researchers identify the number of mutations in the blood of individuals and then monitor them to determine whether those with the most mutations are most likely to develop cancer. That study is now in progress, he said.
