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-cadherins role in stomach
cancer suggests that its role in other cancers should also be explored.