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 May 13, 2005
Gene Mutation Linked to Cancer Risk
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By Amanda Gardner, HealthDay Reporter

WEDNESDAY, April 20 (HealthDay News) -- Researchers have identified a gene mutation that may contribute to certain cancers.

Although the gene does not seem to have as great an effect as other established cancer genes, such as BRCA 1 and 2 in breast cancer, it may be present in a greater number of people, the scientists said.

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. The alternation might be much more widespread than BRCA1 or 2 but have much less effect on the development of cancer," said senior study author Dr. Carlo M. Croce. He is chairman of the department of molecular virology, immunology and medical genetics at Ohio State University and director of the human cancer genetics program at the university's Comprehensive Cancer Center.

The study was led by scientists at Ohio State's Comprehensive Cancer Center, who worked with an international team of researchers. The findings appear in the April 21 issue of the New England Journal of Medicine.

"They've found a gene that affects the baseline risk of developing cancer," said Dr. Julia Smith, director of the Lynne Cohen Breast Cancer Preventive Care Program and head of the breast cancer screening and prevention program at New York University, both in New York City.

"It's not on the order of the BRCA genes, which have a very large effect. 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," Smith added.

The BRCA 1 and BRCA 2 gene mutations increase a woman's risk of breast cancer by about 80 percent.

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

"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," said Dr. Jay Brooks, chairman of hematology/oncology at the Ochsner Clinic Foundation in New Orleans.

BRCA 1 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 patients with different types of familial or sporadic cancers and compared them to samples from 475 healthy people. The study participants included people with chronic myeloid leukemia, thyroid, colorectal, breast, lung and early stage pancreatic cancer, the researchers said.

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 and a member of the Ras superfamily of genes that are involved in regulating cell growth. 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, Croce said, it's possible and simple to screen for this gene. In reality, however, any procedures would have to be approved by the U.S. 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," Croce said.

Smith said: "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 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," Brooks said. "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."

More information

To learn more about the genetic causes of cancer, visit the National Cancer Institute (www.nci.nih.gov ).

SOURCES: Carlo M. Croce, M.D., chairman, department of molecular virology, immunology and medical genetics, Ohio State University, and director, human cancer genetics program, the Ohio State University Comprehensive Cancer Center, Columbus; Julia Smith, M.D., Ph.D., director, Lynne Cohen Breast Cancer Preventive Care Program, and director, breast cancer screening and prevention, New York University, both in New York City; Jay Brooks, M.D., chairman, hematology/oncology, Ochsner Clinic Foundation, New Orleans; April 21, 2005, New England Journal of Medicine

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