|
The same investigators discovered the mutation in 2003. That
research identified nine families with the mutation and concluded
that a German immigrant couple brought the mutation to
North America
in 1727.
1
The latest study includes an additional 32 families and indicates
that the mutation is actually about 500 years old, suggesting that
it arose several generations earlier in Europeans or perhaps in
Native Americans.
Of the 41 families overall, most are clustered in
Kentucky,
Ohio,
and
Texas.
Scientists at the
Ohio
State
University
Comprehensive
Cancer
Center
and
Creighton
University
conducted the study, published April 1, 2008, in the journal
Cancer Research.
“The increased age of the American Founder Mutation means that it
is significantly more prevalent in the United States than
previously thought,” says principal investigator Albert de la
Chapelle, a researcher with Ohio
State’s Human Cancer Genetics program.
“Of interest is that this mutation has not been found in
Europe,
which is tentative evidence, along with hints from family
histories, that it may have arisen in a Native American.”
The new study estimates that the mutation is present in 32,150
Americans as compared with the earlier figure of 18,981. “But
these numbers are theoretical and need to be substantiated by
further work,” de la Chapelle notes.
“This is an important public health concern,” de la Chapelle says,
“because individuals with a Lynch syndrome mutation can benefit
from earlier and more frequent cancer surveillance.”
In addition, he says, a simple, cheap genetic test can detect the
mutation.
Lynch syndrome, also known as hereditary nonpolyposis colon
cancer, is responsible for about one third of hereditary colon
cancers, and almost 3 percent of colon cancer generally, or about
4,500 cases annually in the
United States.
The initial study of nine families showed that the American
Founder Mutation results in the loss of a very specific piece of a
gene called MSH2 (although many other mutations also cause Lynch
syndrome).
The new study linked 27 of the 41 families into seven groups
through genealogic studies.
The age of the mutation was estimated using certain markers along
the DNA located at either end of the mutation. Such patterns of
markers are called haplotypes.
When a new person was identified for the study, the DNA on each
side of the individual’s mutation was tested for the markers,
producing a shared haplotype. The shorter the shared
haplotype, the older the mutation. This information led to the
estimated age of 500 years.
“This data pushed the original founder mutation back to around
1500, plus or minus a number of years,” says coauthor Heather
Hampel, a genetics counselor and researcher with
Ohio
State’s Human Cancer Genetics Program.
“The Pilgrims began arriving in
the 1600s, so the mutation could have arisen first in very early
settlers from
Europe,
or in Native Americans.”
“It’s unclear whether we’ll ever learn who the first person was to
have this mutation,” Hampel says, “but it is clear that the
mutation is much older than we thought and probably more
widespread. For that reason, we feel it is potentially a serious
public health issue, particularly in states such as
Kentucky
,
Ohio
and
Texas
where it is very prevalent.”
Funding from the National Cancer
Institute and the National Science
Foundation supported this research.
The other researchers involved in this study were Mark Clendenning,
Mark E. Baze, Shuying Sun, Kyle Walsh, Sandya Liyanarachchi, Dan
Fix, Victoria Schunemann and Ilene Comeras, all of Ohio State;
Molly Deacon, Jane F. Lynch, Gordon Gong and Henry T. Lynch of
Creighton University ; and Brittany C. Thomas and Stephen N.
Thibodeau of Mayo Clinic College of Medicine. |
