University of Virginia Health System

Gene Mutation Linked To Cancer Risk

Researchers have identified a gene mutation that may contribute to certain cancers, including breast cancer, say researchers in the New England Journal of Medicine.

Although the gene does not seem to have as great an effect as other established cancer genes, such as BRCA1 and BRCA2 in breast cancer, it may be present in a greater number of persons, the scientists say.

The gene may be implicated in such cancers as chronic myeloid leukemia, as well as thyroid, colorectal, breast, lung, or early stage pancreatic tumors.

"We discovered a gene that represents a new class of tumor suppressors," says study author Dr. Carlo M. Croce, director of the human cancer genetics program at Ohio State University Comprehensive Cancer Center.

"The alternation might be much more widespread than BRCA1 or 2 but have much less effect on the development of cancer," Dr. Croce says.

Fitting the Pieces of the Puzzle

Dr. Julia Smith, head of the breast cancer screening and prevention program at New York University says, "They've found a gene that affects the baseline risk of developing cancer.

"It's not on the order of the BRCA genes, which have a very large effect," she says. "This is a much smaller gene and a much smaller mutation. It's an important report, but it's not on the order of the BRCA gene."

The BRCA1 and BRCA2 gene mutations increase a woman's risk of breast cancer by about 80 percent.

Dr. Smith says, "It's becoming clear that there's going to be an interaction of gene products, the effect of the gene on other genes, that is probably very significant in the development of cancer. The discovery itself is only going to change a person's understanding of their own individual risk by a small amount, but we're now getting these little pieces of the puzzle that will all fit together."

The new findings may lead to new screening and treatment strategies, experts say.

"This is very exciting basic research that may ultimately lead to new therapies that protect us from these areas that are weakened in the genetic make-up of individuals susceptible to cancer," says Dr. Jay Brooks, chairman of hematology/oncology at the Ochsner Clinic Foundation in New Orleans.

BRCA1 and 2 are among a small number of genes identified by scientists that predispose a person to cancer. These mutated genes contribute to what are considered hereditary - or inherited - cancers because they can be traced to a specific gene and mechanism.

Many more cancers are familial, meaning they seem to occur more frequently in certain families but, as of yet, no clear genetic mechanism has been implicated.

Scientists had long thought that a particular section of chromosome 13 might hold the clue to various cancers, including some familial cancers.

For this study, the authors analyzed tumor tissue or blood samples from 325 participants with different types of familial or sporadic cancers and compared them to samples from 475 healthy people. The study included persons with chronic myeloid leukemia, thyroid, colorectal, breast, lung, and early stage pancreatic cancer, the researchers say.

Tumor "Suppressor" Gene Identified

One mutation on the ARLTS1 (ADP-Ribosylation Factor-Like Tumor Suppressor 1) gene was nearly three times as frequent in patients with familial cancers and almost twice as high among patients with sporadic or random cancers.

ARLTS1 is a tumor suppressor gene (which regulates cell growth) and a member of the Ras superfamily of genes. The normal gene seeks out and destroys cells that might be about to become malignant. When the gene is altered, however, it loses that ability, giving malignant cells the opportunity to grow and take root.

In theory, Dr. Croce explains, it is possible and simple to screen for this gene. In reality, however, any procedures would have to be approved by the US Food and Drug Administration and covered by insurance to have any real effect.

If a person did have the alteration, "we would have to watch very carefully whether the patient might be developing cancer," Dr. Croce notes.

The finding also underlines the importance of knowing your family history of cancer.

"It is absolutely critical for individuals to know their family history because many cancers run in families," Dr. Brooks says. "We are beginning to see the molecular mechanisms for this susceptibility, but we already have very, very good screening tests for breast, colon, lung, prostate, skin, and other cancers, which make up about 70 percent of cancers."

Always consult your physician for more information.