Stomach Cancer Susceptibility Gene Found in the Maori

NEW ORLEANS--A mutation in the gene for E-cadherin may partly explain the high rate of stomach cancer among the Maori, the indigenous people of New Zealand, Parry Guilford, PhD, a research fellow in the Cancer Genetics Laboratory, University of Otago, Dunedin, New Zealand, reported at the 89th annual meeting of the American Association for Cancer Research.

The Maori get gastric cancer at two to three times the rate of other New Zealanders. This high rate, Dr. Guilford said at a press conference, is due in part to stomach cancer susceptibility genes. Maori families with high rates of stomach cancer have been known for years.

One Family, 30 Stomach Cancer Deaths

To attempt to find one of these susceptibility genes, Dr. Guilford and his colleagues chose a family that had suffered about 30 deaths from stomach cancer in the past 30 years. In this family, people tend to get stomach cancer in their 20s, and almost all die within 6 months of diagnosis. The researchers looked for genetic markers shared by family members with cancer; all markers were near genes that the researchers considered candidates for a susceptibility gene.

The researchers did find some markers--those surrounding the gene for the cell-adhesion protein E-cadherin--that were inherited along with stomach cancer in this family. Analysis and sequen-cing of the gene for E-cadherin in some of the marker carriers revealed that it contained a mutation in the final nucleotide of exon 7.

Dr. Guilford and his colleagues then looked for E-cadherin mutations in two other Maori families with an inherited early-onset stomach cancer. Like the first family studied, the affected members of both families had mutations in theE-cadherin gene, although the location was different in each of the three families. These results were published in a recent issue of Nature (March 26, 1998).

The researchers also calculated that the gene has a penetrance of 70% based on the proportion of people with the mutated gene who developed gastric cancer by the age of 60.

E-cadherin acts to keep cells bound together. Dr. Guilford and his colleagues speculate that a mutation in the gene for E-cadherin makes it easier for tumor cells to migrate.

At a press conference, Dr. Guilford said that this discovery could be important for clinical management. Currently, members of these cancer-prone families are not usually diagnosed with stomach cancers until it is too late for cure. Now, for the first time, it should be possible to test family members for the mutation in the gene for E-cadherin and so determine who is at high risk of developing stomach cancer. These members can be followed carefully and their cancers caught and treated early, he said.

He also noted that the discovery of E-cadherin’s role in stomach cancer suggests that its role in other cancers should also be explored.