A group of scientists at Memorial Sloan-Kettering Cancer Center in New York identified an inherited genetic mutation that could account for up to nine percent of colon cancer cases in the US. The gene mutation also was found in patients with several other types of cancers as well as in healthy individuals. The researchers published their findings in a recent issue of the journal Cancer Research (Vol. 59, No. 22).

The mutation interferes with the activity of a substance called transforming growth factor beta (TGF-b ). Normally, TGF-b inhibits the growth of most normal and cancerous cells. The mutation, called Tb R-I(6A), weakens the cells? response to the growth factor, which then fails to stop cancer cells from growing.

The researchers compared 851 cancer patients to a control group of 735 healthy individuals. Nine (1.1 percent) of the cancer patients inherited one copy of the mutation from each parent, compared with none of the healthy individuals. Of the nine cancers, there were four of the colon, two of the testicles, and one each of the ovaries, lymph nodes, and lung. In addition, 15 percent of the cancer patients carried one copy of the mutation, compared with 11 percent of healthy people.

"To find this number of people in the cancer group who carried two copies of this mutation and no such individuals among the healthy [individuals] is striking evidence for the cancer risk that results," said lead study author Boris Pasche, MD, PhD, a postdoctoral researcher at Memorial Sloan-Kettering Cancer Center.

"The two significant aspects of this finding are the relatively high frequency of this mutation in the general population, and the identification of a new mechanism that may result in increased risk for cancer," added Kenneth Offit, MD, a senior study author and chief of the clinical genetics service at Memorial Sloan-Kettering. Some mutations of other genes confer a greater colon cancer risk than Tb R-I(6A), but are much less common and therefore are responsible for far fewer cases of this disease.

Dawn Willis, PhD, American Cancer Society (ACS) scientific program director, said additional research is needed to determine the medical usefulness of this information.

Dr. Willis believes that studies like the one on Tb R-I(6A) could lead to others that evaluate the usefulness of diet, long-term aspirin use, and earlier and more frequent screening in fighting colon cancer.

For now, she advises against genetic testing for this new colorectal cancer gene. Most doctors still aren?t sure how to interpret the results, according to Dr. Willis.

For people with a strong family history of colorectal cancer, however, testing for other cancer susceptibility genes can identify those who can benefit from more intensive screening or even from preventive removal of the colon.

The ACS estimates 130,200 cases of colorectal cancer (93,800 cases of colon cancer and 36,400 cases of rectum cancer) will be diagnosed in the US this year, and 56,300 people will die of those diseases (47,700 from colon cancer and 8,600 from rectal cancer).