Common Gene Implicated in Many Cancers

Mutation raises overall risk by 26 percent

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HealthDay Reporter

(HealthDay is the new name for HealthScout News.)

THURSDAY, Aug. 28, 2003 (HealthDayNews) -- A study showing that a relatively common genetic mutation increases the risk of many kinds of cancer points toward a future in which routine screening tests could become a common weapon against cancer, researchers report.

The study is part of an important shift in emphasis in research about the role of genetics in cancer. Until recently, researchers have concentrated on what are called "high-penetrance" genes, relatively rare mutations that greatly increase the risk of specific cancers.

Now they are more and more looking at more common "low-penetrance" genes that somehow interact with environmental factors to increase the risk of many different cancers.

The new study, reported in the Sept. 1 issue of the Journal of Clinical Oncology by researchers at Northwestern Memorial Hospital in Chicago, says a mutation in a gene for a protein called transforming growth factor beta (TGF-beta) increases the risk of all cancers by 26 percent.

The TGF-beta mutation may increase the risk of breast cancer by 48 percent, ovarian cancer by 53 percent, and colon cancer by 38 percent, the researchers say, with comparable increases in other malignancies.

Those risk estimates were produced by amassing data from seven studies that looked at the incidence of the TGF-beta mutation in more than 2,000 patients with many kinds of cancer, says study author Dr. Virginia G. Kaklamani, an oncologist at Northwestern Memorial.

The TGF-beta mutation is an obvious candidate for a cancer risk factor because the gene plays an important role in "a pathway that is important in cancer development in general," says Kaklamani. "In normal cells, it inhibits growth. When normal cells become transformed to cancer cells, the mutation we are talking about decreases that signal, so that it acts as a growth factor."

After animal studies showed the mutation played a role in many cancers, Dr. Boris Pasche, then at Memorial Sloan-Kettering Cancer Center in New York City and now at Northwestern, began the analysis of human studies that resulted in the new report.

Now the Northwestern researchers are doing studies in which carriers of the mutation are being identified and followed to determine their risk of cancer. "In the future, we hope that we can identify individuals at high risk because they carry the mutation," Kaklamani says.

The ultimate goal is to develop a model that includes a large number of low-penetrance mutations and would assess overall cancer risk with a single genetic test, she says.

It's a long-term goal, says Dr. Loren S. Michel, a research fellow at Memorial Sloan-Kettering and a member of the research team, because "finding these common genes has not been easy." The new study is important because it is one of a very few that have identified low-penetrance candidates, he says.

That is not an easy job, he says. First comes laboratory work in which "one does a lot of DNA sequencing and tries to find polymorphisms [mutations] that predispose to cancer," Michel says. "Then you go through a huge number of patient samples and find whether this gene is at a very high frequency in a cancer population and in people who do not yet have cancer."

The effort is being pushed in a number of laboratories because "finding these genes is going to be the frontier in cancer biology, giving us a new understanding of how cancer develops," Michel says.

More information

Get an overview of cancer genetics from the National Cancer Institute or the Medical College of Wisconsin.

SOURCES: Virginia G. Kaklamani, M.D., oncologist, Northwestern Memorial Hospital, Chicago; Loren S. Michel, M.D., research fellow, Memorial Sloan-Kettering Cancer Center, New York City; Sept. 1, 2003, Journal of Clinical Oncology

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