Genetic test for colon cancer under way.

Just 6 months after two separate research teams announced the chromosomal home of MSH2, the first gene discovered for one common form of colon cancer (SN: 12/11/93, p.388), Richard Fishel has even better news: a bioassay that will tell high-risk individuals if they are likely to develop the inherited disease.

Fishel, a member of one of the MSH2 teams, is a molecular biochemist at the University of Vermont Medical School in Burlington. He announced the new test last week at the General Motors Cancer Research Foundation Scientific Conference held at the National Institutes of Health in Bethesda, Md. The new test, or bioassay, is intended for people at risk of hereditary nonpolyposis colorectal cancer (HNPCC), one of the most commonly inherited cancers in humans.

The same genetic defect can also contribute to cancers other than that of the colon: ovarian, uterine, endometrial, lung, stomach, and others.

"We now have the unparalleled opportunity to help 23,000 Americans yearly who develop cancer as a result of inheriting a defective MSH2 or MLH1 gene," Fishel says. Both these genes can contribute to HNPCC, he points out. His group now links a third, as-yet-unreported gene to colon cancer. All three were originally discovered in yeast cells and affect DNA production.

In healthy yeast cells, a repair protein called MSH2 fixes glitches in the genetic alphabet, Fishel says, a process akin to a computer's spell-checker. When the gene that controls MSH2 is defective, there's nothing to check DNA "spelling," thus creating faulty DNA full of "spelling errors." Fishel points out that his team is ahead of the cancer game because of 20 years of basic research done with yeast. "We already knew how these genes functioned."

Currently, there exists a blood test that determines only the presence of a genetic alteration. However, Fishel says, his bioassay can determine the presence of a functional alteration, which has shown -- in "the handful of families" he's worked with so far -- to predict cancer.

"We might encourage predisposed individuals to alter their lifestyle," Fishel says. "High-fiber, low-fat diet."

High-risk individuals who don't carry the functional mutations can breathe easier. "Those individuals don't have to be screened by colonoscopies every year, don't have to be encouraged to alter their lifestyle. They basically can lead normal lives, and that reduces health care costs," Fishel adds.

Though the bioassay results are preliminary, they are also promising. Says Richard Kolodner, a researcher at the Dana-Farber Cancer Institute in Boston who worked with Fishel on the MSH2 gene: "The data that have come along... are convincing enough that companies that do commercial testing are starting to work on developing tests.... And that's happened in a year."

"Combining genetic diagnostics with bioassays," says Fishel, "is the wave of the future."