Genetic basis of colon cancer.

Genetic basis of colon cancer 

Two new studies provide the clearest picture yet of the specific chromosomal changes leading to colorectal cancer -- cancer of the lower portion of the gastrointestinal tract -- and the important role heredity plays in determining an individual's likelihood of getting the disease.

The two studies, described in the Sept. 1 NEW ENGLAND JOURNAL OF MEDICINE, promise no immediate improvement in diagnosis or treatment. They do suggest, however, that genetic analysis may someday identify those individuals likely to develop the disease. For now, the researchers say, the strong hereditary link confirms that first-degree relatives of patients with colorectal cancer should be especially diligent about getting screened for early evidence of the disease.

The National Cancer Institute recommends that even those individuals without hereditary risk factors should have rectal examinations annually after age 40 and colonoscopic visual exams every three years after age 50. Colorectal cancer claims the lives of about half of those afflicted.

Bert Vogelstein of the Johns Hopkins School of Medicine in Baltimore and his colleagues looked for four specific genetic alterations in 172 specimens of colorectal tumors that had progressed to various stages. Their analysis confirmed previous findings that about half of the more advanced tumors had mutated versions of the so-called ras gene -- a gene that has often been associated with tumor formation. Other chromosomal changes were associated with intermediate stages of tumor formation. Their research suggests that colorectal cancer is often the result of a series of mutations that both trigger the ras gene and cripple one or more genes that normally confer cancer protection.

In many cases, no ras mutations were found, indicating that researchers have yet to find some important pieces of the cancer's genetic puzzle. Previous research has shown that environmental factors -- in particular a high-fat, low-fiber diet -- can influence colorectal carcinogenesis.

In the second study, Lisa A. Cannon-Albright and her colleagues at the University of Utah Medical Center in Salt Lake City did pedigree studies of 670 individuals who had at least one relative with a precancerous polyp or colonic cancer. They conclude that an inherited susceptibility to precancerous polups and colorectal cancer is responsible for the majority of colonic cancers seen clinically. They predict that ongoing genetic and lifestyle studies will allow researchers to identify environmental and dietary factors that may help trigger cancer formation in susceptible individuals.