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$Unique_ID{BRK03955}
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$Title{Lynch Syndromes}
$Subject{Lynch Syndromes Hereditary Nonpolyposis Colorectal Cancer Lynch
Syndromes I & II Hereditary Nonpolyposis Colorectal Carcinoma Lynch Syndrome I
Hereditary Site Specific Cancer Lynch Syndrome II Cancer Family Syndrome
Familial Polyposis Crohn's Disease Peutz-Jegher's Syndrome Carcinoid Syndrome
}
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Copyright (C) 1993 National Organization for Rare Disorders, Inc.

953:
Lynch Syndromes

** IMPORTANT **
It is possible that the main title of the article (Lynch Syndromes) is
not the name you expected.  Please check the SYNONYM listing to find the
alternate names and disorder subdivisions covered by this article.

Synonyms

     Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndromes I & II)
     Hereditary Nonpolyposis Colorectal Carcinoma

Disorder Subdivision:

     Lynch Syndrome I (Hereditary Site Specific Cancer)
     Lynch Syndrome II (Cancer Family Syndrome)

Information on the following diseases can be found in the Related
Disorders section of this report:

     Familial Polyposis
     Crohn's Disease
     Peutz-Jegher's Syndrome
     Carcinoid Syndrome

General Discussion

**REMINDER **
The Information contained in the Rare Disease Database is provided for
educational purposes only.  It should not be used for diagnostic or treatment
purposes.  If you wish to obtain more information about this disorder, please
contact your personal physician and/or the agencies listed in the "Resources"
section of this report.

The Lynch Syndromes are rare hereditary disorders that usually cause
cancer to develop either in the colorectal area or in other sites.  Primary
cancers may develop in the female genital tract, stomach, brain, breasts, or
urological system.  The cancers of the colorectal area associated with the
Lynch Syndromes usually develop at a younger age than is normally found in
other persons with such cancers.

Symptoms

The Lynch Syndromes are characterized by rare, hereditary cancers that
develop at a younger age than normal usually in the colorectal area or in
close by areas such as the pancreas.  Primary cancers can also develop in
other areas of the body in persons of any age who have the genes that
predispose a person to the development of these cancers.  Rectal bleeding,
diarrhea, abdominal pain, and weight loss are usually the first signs when
Lynch Syndrome is present.  When examined by a doctor polyps or growths in
the mucous lining of the small bowel are usually present.

Lynch Syndrome I is characterized by hereditary cancers that usually
develop in the rectum or colon or in closely related areas such as the small
bowel.

Lynch Syndrome II is characterized by cancers that develop in the
colorectal area or in other sites throughout the body.

Often the first sign of the probable development of colorectal cancer is
the growth of polyps in the colon or rectum which may be accompanied by pain
or bleeding.  These polyps are not associated with the growth of multiple
polyps as in the disease known as Familial Polyposis (for more information on
this disorder, choose "Polyposis" as your search term in the Rare Disease
Database).  Often the polyp is the first sign that cancer may develop later,
especially if other family members have developed colon or rectal cancer.  It
is also an important sign if these cancers occur at a younger than normal age
(colorectal cancer usually occurs after the age of sixty).  In some people
with this disorder cancer will develop in areas other than the colorectal
area such as:  the urological system, brain, stomach, breasts, or female
genital tract.

Causes

The Lynch Syndromes are rare cancers believed to be inherited because of a
autosomal dominant genetic predisposition (a genetic predisposition means
that a person may carry a gene for a disease but it may not be expressed
unless something in the environment triggers the disease).

Human traits, including the classic genetic diseases, are the product of
the interaction of two genes, one received from the father and one from the
mother.  In dominant predispositions a single copy of the disease gene
(received from either the mother or father) may be expressed "dominating" the
other normal gene and if environmental conditions trigger the gene it can
result in the appearance of the disease.  The risk of transmitting the gene
from affected parent to offspring is fifty percent for each pregnancy
regardless of the sex of the resulting child.

Some researchers believe that the location of the gene that may be
responsible for these forms of hereditary cancers is located on the long arm
(q) of the 18th chromosome.  More study is necessary to determine if this
theory is accurate.

Affected Population

The Lynch Syndromes affect 5 to 6% of all of the diagnosed forms of
colorectal cancers involving 160,000 new cases annually in the United States.
The average age of the Lynch syndrome patient is ten to twenty years younger
than the average age of most colorectal cancer patients (in the sixth
decade).  Other forms of cancer associated with the Lynch Syndrome can occur
at any age.

Related Disorders

Symptoms of the following disorders can be similar to those of Lynch
Syndromes.  Comparisons may be useful for a differential diagnosis:

Familial Polyposis is a hereditary condition characterized by multiple,
benign growths (polyps) that develop during puberty in the mucous lining of
the gastrointestinal tract.  Although the polyps themselves are initially
benign, (non-cancerous) untreated patients with Familial Polyposis will
eventually develop cancer of the large bowel, often during their late
thirties or an earlier age.  (For more information on this disorder, choose
"Polyposis" as your search term in the Rare Disease Database).

Crohn's Disease is a form of inflammatory bowel disease characterized by
severe chronic inflammation of the wall or any part of the gastrointestinal
tract.  Pain, bloating, and diarrhea are often present.  A solid mass may
often be felt (palpated) in the abdomen.  Fissures, abscesses, scarring,
obstruction to varying degrees, and fistulas develop as a result of the
chronic inflammation.  (For more information on this disorder, choose "Crohn"
as your search term in the Rare Disease Database).

Peutz-Jeghers Syndrome is a hereditary condition characterized by
multiple, benign growths (polyps) on the mucous lining of the intestinal
wall, and dark discolorations on the skin and mucous surfaces.  Low grade
malignancies develop in about a fifth of the patients.  (For more information
on this disorder, choose "Peutz-Jeghers" as your search term in the Rare
Disease Database).

Carcinoid Syndrome is a rare, malignant disease affecting the small
bowel, stomach and/or pancreas.  Very slow growing tumors can spread
(metastasize) to the liver, lungs, and ovaries.  Major symptoms include
diarrhea, flushing, and wheezing.  (For more information on this disorder,
choose "Carcinoid" as your search term in the Rare Disease Database).

Therapies:  Standard

The Lynch Syndromes are treated by surgery to remove the colon (colectomy).
Other measures that can be taken by members of a family affected by Lynch
Syndrome are to begin having examinations of the colon (colonoscopy) at an
early age (e.g., 25 years of age) or earlier if malignant polyps have been
found; every two to three years; and tests to determine if blood is found in
the stool (fecal occult blood test) should be done at this time also.
Education about these rare inherited forms of cancer is important to help
family members become aware of the possibilities for disease and the need for
frequent medical examinations.

Genetic counseling will be of benefit for patients and their families.
Other treatment is symptomatic and supportive.

Therapies:  Investigational

Investigational drugs being developed for the treatment of colorectal cancers
include fluorouracil with interferon alfa-2a, which is being developed by
Hoffmann-LaRoche Inc.

In the treatment of colorectal cancers that have metastasized to other
locations in the body other drugs are being tested including:  anti-TAP
immunotoxin being developed by Xoma Corporation, disaccharide tripeptide
glycerol dipalmitoyl by Immuno Therapeutics, Inc., Leucovorin adjunct with
fluorouracil 2,3 by Burroughs Wellcome Co., Levoleucovorin with fluorouracil
by Lederle Laboratories, and trimetrexate glucuronate 2,5 by U.S. Bioscience,
Inc.

Further studies are also being carried out to determine the exact
location of the gene that causes these inherited forms of colorectal cancers.
It is hoped that a genetic test will be developed to identify people
susceptible to the Lynch Syndromes, and preventive measures may be developed.

The National Institutes of Health (NIH) is sponsoring the Human Genome
Project which is aimed at mapping every gene in the human body and learning
why they sometimes malfunction.  It is hoped that this new knowledge will
lead to prevention and treatment of genetic disorders in the future.

This disease entry is based upon medical information available through
June 1993.  Since NORD's resources are limited, it is not possible to keep
every entry in the Rare Disease Database completely current and accurate.
Please check with the agencies listed in the Resources section for the most
current information about this disorder.

Resources

For more information on Lynch Syndromes, please contact:

     National Organization for Rare Disorders (NORD)
     P.O. Box 8923
     New Fairfield, CT  06812
     [phone]

     American Cancer Society
     1599 Clifton Rd., NE
     Atlanta, GA  30329
     [phone]

     NIH/National Cancer Institute (NCI)
     9000 Rockville Pike, Bldg. 31, Rm. 1A2A
     Bethesda, MD  20892
     (800) 4-CANCER

The National Cancer Institute has developed PDQ (Physician Data Query), a
computerized database designed to give the public, cancer patients and
families, and health professionals quick and easy access to many types of
information vital to patients with this and many other types of cancer.  To
gain access to this service, call:  Cancer Information Service (CIS) 1-800-4-
CANCER In Washington, DC and suburbs in Maryland and Virginia, 636-5700 In
Alaska, 1-800-638-6070 In Oahu, Hawaii, 808-524-1234 (Neighbor islands call
collect).

For Genetic Information and Genetic Counseling Referrals:

     March of Dimes Birth Defects Foundation
     1275 Mamaroneck Ave.
     White Plains, NY 10605
     [phone]

     Alliance of Genetic Support Groups
     35 Wisconsin Circle, Suite 440
     Chevy Chase, MD 20815
     (800)-336-GENE
     [phone]

References

MENDELIAN INHERITANCE IN MAN, 10th Ed.:  Victor A. McKusick, Editor:  Johns
Hopkins University Press, 1992.  Pp. 180-181, 183-184.

GASTROINTESTINAL DISEASE, PATHOPHYSIOLOGY DIAGNOSIS MANAGEMENT, 4th Ed.:
Marvin H. Sleisenger, W.B. Saunders Co., 1989.  Pp. 1525-1528.

THE MOLECULAR BASIS OF COLON CANCER., Rustgi, A.K., et al.; Annu Rev Med,
1992, (issue 43).  Pp. 61-68.

GENETICS OF COLON CANCER, Ahnen, D.J., West J Med, June, 1991, (issue 154
(4)).  Pp. 700-705.

HEREDITARY NONPOLYPOSIS COLORECTAL CANCER (LYNCH SYNDROMES I & II).
GENETICS, PATHOLOGY, NATURAL HISTORY, AND CANCER CONTROL, PART I., Lynch,
H.T., et al.; Cancer Genet Cytogenet, June, 1991, (issue 53 (2)).  Pp. 143-
160.

ADENOCARCINOMA OF THE SMALL BOWEL IN LYNCH SYNDROME II., Lynch, H.T., et
al.; Cancer, November 15, 1989, (issue 64 (10)).  Pp. 2178-2183.

THE LYNCH SYNDROME II AND UROLOGICAL MALIGNANCIES., H.T. Lynch, et al.; J
Urol, January, 1990, (issue 143 (1)).  Pp. 24-28.