0 .MIMIO.A. WaiSMA, MMIMSW:MUSW.n•VAMMW.MMWM:`;?,',,,MUMM.M.M.MrAMMWM,MM'..,M,W

• M.MMAteX,'AW:.,a:W.MVatkUs3VK:..'WM.=.W.:IWV,MVM'MVWZ:WM'MKMMMVA18M,'•..raMei',',:VMrt:M,..WMT•EV.V.F..4:ae,AVMMW:air•XMZM.'t'ra,K%r21M.VZZVFRWMU?N?e22ia

Discovery

Of A
Lifetime

Johns Hopkins' findings may benefit thousands of Ashkenazi
Jews at risk of contracting colorectal cancer.

CHRISTINE STUTZ SPECIAL TO THE JEWISH NEWS

R

esearchers at the Johns
Hopkins Oncology Center
in Baltimore have identi-
fied a genetic mutation
that is responsible for about 12
percent of colorectal cancer cas-
es among Ashkenazim, or Jews
of European descent.
The mutation can be detected
by a simple blood test, which re-
searchers are recommending for
any Jewish person with a fami-
ly history of colorectal cancer.
The researchers believe those
with the mutation — about
700,000 Jews internationally —
have an estimated 12-15 percent
lifetime risk of developing col-
orectal cancer.
Dr. Bert Vogelstein, co-direc-
tor of the Molecular Genetics
Lab at Hopkins, and his team
published their findings in the
September 1997 issue of the
journal Nature Genetics. Dr. Vo-
gelstein emphasized that the
findings are good news for
Ashkenazi Jews because, with
proper surveillance, colorectal
cancer is easily prevented.
`There should be no reason to
die from this disease, or even to
get seriously ill from it," he said.
Biannual colonoscopies, internal
exams during which precancer-
ous polyps can be detected and
removed, are an effective method
of preventing colorectal cancer,
said Dr. Vogelstein, who is Jew-
ish.
He noted that this is the first
example of a genetic test being
developed for a disease that is
preventable.
Hopkins was flooded with
phone calls and faxes after news
of the discovery made the front
pages of the nation's newspapers

last week and led off television
and radio news broadcasts.
While the results of the dis-
covery are "pretty exciting," one
must exercise caution in inter-
preting them, said Dr. Francis
Collins, director of the National
Human Genome Research In-
stitute at Bethesda's National
Institutes of Health.
The approximate twofold risk
of developing colorectal cancer
for those carrying the mutation
should be considered a prelimi-
nary estimate pending further
research, Dr. Collins said. He
pointed out that the risks asso-
ciated with two breast cancer
genes — BRCA1 and BRCA2 —
were initially overestimated.
Dr. Collins also urged those
considering genetic testing to
consider the risks involved, as
well as the benefits. Insurance
companies and employers have
been known to discriminate
against individuals found to
have a genetic predisposition to
disease, he said. News of a ge-
netic mutation also can strain
family relations, he said.
A larger issue of concern to
him is the possible stigmatizing
of the Jewish community fol-
lowing discoveries of hereditary
tendencies to certain illnesses.
"I'm worried that this will cre-
ate the impression among the
public that colon cancer is a Jew-
ish disease, or breast cancer is a
Jewish disease," Dr. Collins said.
Scientists tend to study ho-
mogenous populations, such as
Mormons, the Amish and Ashke-
nazi Jews, because they have
been geographically -and social-
ly isolated. Because they tend to
marry within their own group,

Dr. Bert
Vogelstein:
An important
coincidence.

he said, their genetic makeup is
more homogeneous, and there-
fore easier to study.
This homogeneity also allows
genetic anomalies to perpetuate
themselves.
The colon cancer gene in ques-
tion — called APC — is one that
the same team of Hopkins re-
searchers first discovered in
1991. But the new mutation is
different from any that has been
seen previously. This new mu-
tation does not, itself, cause col-
orectal cancer, Dr. Vogelstein
explained. It's during the copy-
ing of that gene, a phenomenon
that occurs daily in every colon
cell, that a second error can oc-
cur that can render the APC
gene dysfunctional.
Because the APC gene sup-
presses tumor growth, an error
in this gene causes uncontrolled
cell division. And that's what
produces a tumor.
Their finding is significant not
only because it provides impor-
tant health information for the
Jewish community, Dr. Vogel-
stein said. It also indicates to sci-
entists that other mutations
previously thought to be harm-
less might, in fact, cause cancer.
Dr. Vogelstein and his colleagues
believe subsequent studies will
find similar mutations in other
genes that cause other types of
cancer.

According to Dr. Vogelstein, ponent, Dr. Vogelstein said. But
this discovery was initiated ac- it has been difficult for re-
cidentally. About two years ago, - searchers to determine the ex-
a man with cancer came to the act role of heredity, because
Molecular Genetics Lab, want- family members also tend to
ing to know if he had a mutation share certain environmental fac-
of the APC gene. While study- tors, such as diet and exposure
ing his genetic makeup, the re- to toxic substances.
searchers found a deviation, but
More than 130,000 cases of
they believed it was harmless.
colon cancer are diagnosed in
Later, while studying anoth- the United States each year,
er individual, Dr. Vogelstein's said Dr. Vogelstein. Between 15
team found the same variation. and 50 percent of those cases are
It occurred to Dr. Vogelstein believed to have a hereditary
that both men were Ashkenaz- component; of those, familial col-
icJews.
orectal cancer is the most corn-
The researchers tested 766 mon. Another 3-5 percent of
Ashkenazim and found 47 — colon cancers are caused by spe-
about 6 percent — with the mu- cific inherited syndromes, and
tation. To provide a basis for the remaining cases occur with-
comparison, 1,000 non-Ashke- out any apparent hereditary
nazi Jews were tested, and none component.
had the mutation.
Although the gene mutation
At that point, Dr. Vogelstein so far has appeared only in
said, he and his team still didn't Ashkenazi Jews, offspring of
believe the mutation was can- marriages between Ashkenaz-
cer-causing. They examined the im and Sephardim -- Jews of
blood of Ashkenazim with colon African, Asian, South American
cancer and found that one-third or Spanish extraction— or of in-
of those with colon cancer in termarriages, are also at risk of
their families had the mutation. inheriting the gene if the Ashke-
"This should have been one of nazic parent carries it, he said.
nature's secrets," he said. It was
Because all humans are at
only discovered as a result of some risk of developing colon
comparing the genes of two men cancer, Dr. Vogelstein said, the
who turned out to be Ashke- best precautions continue to be
nazim.
a high-fiber, low-fat diet con-
A high number of colorectal taining little red meat, and reg-
cancers have a hereditary com- ular medical examinations. ❑