PHILADELPHIAA simple new test can detect which
individuals may be at risk for hereditary nonpolyposis colon cancer
(HNPCC), or Lynchs syndrome, and therefore should undergo
genetic screening for HNPCC mutations.
The test, which analyzes a type of genetic instability known as
microsatellite instability, offers greater accuracy than current
clinical parameters, Tao Liu, MD, of the Karolinska Institute,
Stockholm, Sweden, said at the annual meeting of the American
Association for Cancer Research (AACR).
Dr. Liu said that up to 5% of the general population is estimated to
have an HNPCC mutation. The current clinical definition of HNPCC, he
continued, is the occurrence of colon cancer in at least three
individuals from one family over at least two generations and with at
least one individual diagnosed under age 50. Most cases,
he said, are due to alterations in one of the genes responsible
for repairing mistakes in newly copied DNA.
Tumors from HNPCC patients are characterized by a genetic instability
in segments known as microsatellites. The study evaluated affected
members from 83 unrelated colorectal cancer families. A mutation was
found in 71% of the families whose tumors showed microsatellite
instability, but in only 1 of 35 families (2.9%) with stable tumors.
The finding of microsatellite instability in colorectal tumors
from patients with a family history of colorectal cancer or an early
onset of disease is the best predictive indicator of a germ-line
mutation, Dr. Liu said.
Must Have a Family History
The test cannot preselect gene carriers among sporadic cases.
However, he said, in patients with a family history
of colorectal cancer, a test for microsatellite instability can
predict a gene carrier, and very few germ-line mutations will remain undetected.
Identification of gene carriers, he concluded, allows genetic testing
in their families. Gene carriers can be offered surveillance,
and the noncarriers can be informed that they are at no increased
risk, Dr. Liu said.