Gene May Predispose Some Families to Cancer

Gene Variation Linked to Increased Risk of Some Familial Cancers

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April 20, 2005 -- Scientists say they've spotted a gene that may explain some cases of familial cancer. Those are multiple cancers in one family that cannot be explained by inheritance.

The gene, dubbed ARLTS1, appears to play a role in suppressing tumors, researchers report in The New England Journal of Medicine. A glitch in that gene might affect vulnerability to cancer, the study shows.

One day "in the near future," genetic testing might screen for the gene (and others), says Carlo Croce, MD, in a news release. Croce worked on the study and directs Ohio State University's Human Cancer Genetics Program.

'Subtle' Effect

An abnormally functioning ARLTS1 gene doesn't seem to guarantee that a person will get cancer, but it may nudge them in that direction.

Most geneticists say that less than 5% of cancers are inherited, according to the news release. Environmental influences (such as smoking, diet, weight, and exposure to cancer-causing substances) are also important.

A handful of genes have been flagged for cancer connections, such as the BRCA1 and BRCA2 genes, which are strongly linked to breast cancer.

ARLTS1 may be one of a second string of genes that are beginning to draw attention.

"ARLTS1 is one of an emerging set of genes whose effects are subtle, but which still play an important and predictable role in the development of cancer in some people," says George Calin, MD, PhD, in the news release.

Calin worked on the study while at Thomas Jefferson University in Philadelphia. He now works with Croce at Ohio State University.

Hunting for ARLTS1

The researchers studied DNA from 800 European and U.S. participants. They analyzed tumor or blood samples from 325 people with sporadic or familial cancers. DNA from the other 475 participants -- who did not have cancer -- was screened for comparison.

Patients included those with thyroid, breast, prostate, lung, colorectal, and skin cancer (melanoma). Others had chronic lymphocytic leukemia, pancreatic cancer, or idiopathic pancytopenia (a decreased number of blood cells).

The ALRTS1 mutation was significantly more common in the familial cancer group than with sporadic cancers or cancer-free participants.

The ARLTS1 mutation was seen nearly three times more frequently in familial cancer patients than in people without cancer. The mutation also occurred nearly twice as often with sporadic cancers as it did in cancer-free participants.

Not a Smoking Gun

The gene mutation seemed to skew toward familial cancer without making cancer a sure thing.

"A genetic variant of ARLTS1 predisposes patients to familial cancer," write researchers.

They conclude that ARLTS1 accounts for a small percentage of familial melanoma or familial chronic lymphocytic leukemia cases.

Show Sources

SOURCES: Calin, G. The New England Journal of Medicine, April 21, 2005; vol 352: pp 1667-1676. News release, Ohio State University.
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