Sanford R. Weiss, MD Center for Hereditary Colorectal Neoplasia

Toll-Free: 866.320.4573

Call Us Toll Free:

800.223.2273 x47000

Greetings!

Welcome to the website of the Sanford R. Weiss, MD, Center for Hereditary Colorectal Cancer. We are happy that you visited us. The purpose of this site is to provide helpful information about the syndromes of inherited colorectal cancer.

Only 5% of all cases of colorectal cancer are hereditary, where a mutated gene causes the cancer and can be passed down from a parent to a child. Inherited colorectal cancer, like other inherited cancers, is an accelerated version of regular cancer. It comes on younger, it can occur in more than one place in the colon and cancer can affect several different organs. Inherited cancer runs in the family so there is often a strong family history. It is very important to diagnose inherited colorectal cancer when it is present, because then there is the opportunity to screen family members by genetic testing, and to prevent cancer by timely testing and treatment.

It is our mission at the Sanford R. Weiss, MD, Center for Hereditary Colorectal Cancer to prevent deaths from inherited colorectal cancer, and we dedicate ourselves to this task every day. In fulfilling our mission we develop a partnership with our patients, their families and their family physicians. It is important that our patients follow suggested appointments and treatment, to the best of their ability. On our part we are always ready to accommodate special requests and circumstances, and are used to helping families from all over the United States and the world.

While we work hard to diagnose, test, treat and follow-up our patients, we are also concerned with education and research. At this time of easy access to media there is a lot of dangerous misinformation available to patients that tends to confuse and dilute what is correct and important. We have developed resources for patients and families that provide reliable, important and helpful information about the syndromes we treat. We also take seriously our task of educating other healthcare providers, and have important leadership roles in national and international societies. Our registry is one of the largest in the world, is backed by years of experience and offers the highest levels of expertise. Our role is to set the standard of excellence of care of patients with inherited colorectal cancer.

Research is the third pillar of our practice. Hereditary colorectal cancer syndromes are uncommon, and there is much that is not known. We have the privilege of caring for large numbers of affected patients, and also the responsibility of using our experience to further the knowledge of these conditions.

Finally, hereditary colorectal cancer is a serious condition. While it can feel unsettling to know you are at risk, we at the Sanford R. Weiss, MD, Center for Hereditary Colorectal Cancer are available to help you maintain your life to the fullest. Accessing this website is the start. We are glad you are here.

Sincerely,
James M. Church, MD
Director, David G. Jagelman Inherited
Colorectal Cancer Registries

The Sanford R. Weiss, MD, Center for Hereditary Colorectal Neoplasia (The Weiss Center) is made up of health care providers from multiple disciplines, who are dedicated to the care of patients with or at risk for hereditary colorectal cancer syndromes. In 1979, Dr. David G. Jagelman established Cleveland Clinic’s Familial Polyposis Registry. His intent was to follow high-risk colorectal patients and families with a personal and/or family history of inherited colorectal cancer. In 1989 Dr. Jagelman left and his role was taken by Dr. James Church. At that time, Hereditary Non Polyposis Colorectal Cancer was added to the registry. In 2008 The Weiss Center was established after receiving an endowment from Sanford R. Weiss M.D., who was a patient of ours with FAP.

The mission of The Jagelman Registry and The Weiss Center is to prevent death from colorectal cancer or cancer of other organs involved in these syndromes by excellent patient care, effective education, and clinically relevant research.

Patient Care

  • To identify patients at high risk for colorectal cancer by virtue of their family history or tumor genetics
  • To advise such patients of their risk and help in selection of appropriate screening tests and therapy
  • To provide specialized counseling and genetic testing where appropriate
  • To act as a patient advocate, and facilitate testing, counseling, and treatment appointments

Cleveland Clinic is committed to identifying patients who may have Lynch syndrome by a routine screening process of patient tissues. The Digestive Disease Institute, Genomic Medicine Institute, Pathology and Laboratory Medicine Institute, and Women’s Health Institute have collaborated to screen all colorectal and endometrial cancers that are surgically removed at Cleveland Clinic for Lynch syndrome by microsatellite instability (MSI) and/or immunohistochemistry (IHC) testing. Routine screening of colorectal cancers with MSI or IHC was initially recommended in 2009 by the Evaluation of Genomic Applications in Practice and Prevention (EGAPP).

The Weiss Center also holds specialized multidisciplinary clinics for patients with hereditary colorectal syndromes. Physicians and care givers work together to provide a team approach to patients and families to facilitate screening and interventions as needed.

Education

  • To educate patients and their families on the nature and implications of inherited colorectal cancer
  • To educate physicians and other healthcare professionals about the basics of colorectal cancer genetics and their clinical implications
  • To encourage and foster the development of inherited colorectal cancer registries throughout this country and the world

As part of our commitment to educating patients about the importance of family history, we developed an online risk assessment that asks questions about personal and family history of colon polyp and cancer to determine an individual’s risk of developing colorectal cancer and subsequently provide them with recommended screening options.

Research

  • To carry out clinically important research on inherited colorectal cancer syndromes

The cornerstone of the Weiss Center is the David G. Jagelman Inherited Colorectal Cancer Registries. Here are some frequently asked questions about the Registries.

»What is a registry?

A registry is a database of patients and families with hereditary colorectal cancer that forms the basis of patient care, education and research. It allows coordination and integration of care and its site is the setting where patients and families can meet with specialists.

»What is the role of the registry?

The main role of a registry is to allow for effective coordination of evaluation and care of patients at high familial risk of colorectal cancer. The aim is cancer prevention. In addition, a registry:

  • Promotes the knowledge of the risks and implication of a family history of colorectal cancer
  • Provides the best care to patients and families
  • Conducts research

The registry will:

  • Educate patients and their families about the disease, tests, surgery options, surveillance protocols and studies
  • Refer patients and families to meet with a genetic counselor for genetic consult
  • Provide support and counseling
  • Ensure that patients receive the best care
»How can a registry help?

The registry educates patients and their families, provides support and counseling, and ensures that patients receive the appropriate care needed to live a long healthy life.

Education:

The Registry provides patients and their families information about their disease. The coordinators will help patients and families understand who is at risk, and what type of surveillance testing should be done and when. The registry coordinators will also review the different types of procedures, procedure instructions, different types of surgical options as well as current clinical trials available to patients and families.

Support and Counseling:

The Registry will be a resource for patients and their families if they have questions regarding their disease. The coordinators will also be available to listen to patients when they need to talk and to provide patients with questions to ask their physicians when looking for the best care at outside facilities when unable to be seen at Cleveland Clinic. The Registry encourages patients to educate themselves on their disease and will provide patients with the available resources to do that. The coordinators also encourage patients to meet with genetic counselors to discuss in greater detail the benefits of genetic testing and how that will affect the whole family.

Patient Care:

The Registry coordinators will help facilitate patients in making their initial appointments with the appropriate specialists as well as scheduling appointments in our hereditary caner “High Risk Clinic.” Coordinators will be available to patients before, during and after physician appointments to answer questions. Patients in the Registry receive reminders of annual examinations, and coordinators can assist patients in making follow up appointments and test.

»How do I join the Registry at Cleveland Clinic?

A patient needs to talk with a registry coordinator, who will take a family history to determine if participation in the registry is appropriate. This can be done in person or over the phone. Once eligibility for participation is determined, a coordinator will discuss the consent form for participation. The consent form summarizes information on the registry, risks and benefits, confidentiality, and voluntary participation. If the patient is interested in participation, verbalizes an understanding and has no questions they can sign the consent, when being seen in person. An original copy of the consent is kept on file with the registry and one copy is given to the patient. If the patient is not seen in person then the registry coordinator will mail out a study fact sheet to the patient with a medical release form that is accompanied with an envelope to be completed and sent back to the registry. Once received the patient is enrolled into the registry.

Being in a registry does not affect your care with your own physician. It is important to note that patients in a registry are still under the care of their referring doctors. Registries do not assume the care of its participants. The main role of the registry is to educate and support patients.

»What information will the Registry need?

Once a consent form is signed, a confidential chart is started which consists of 6 parts; a pedigree (a family tree), clinical records, diagnostic test results, correspondence, outside records and the original signed consent form. The Registry will collect all records regarding medical and surgical treatment pertaining to the disease. Every patient will sign a medical release form to help us gather the patient’s outside records. The Registry will also collect death certificates on deceased family members to confirm the actual cause of death. The Registry will do an extensive personal and family history by developing a family pedigree, which will be an ongoing project since families are continually changing.

»What is done with this information?

All records obtained by the Registry are kept in a confidential chart. Each family is assigned a Registry identification number and each member of that family is given a patient number. All records collected are filed in a family chart under the appropriate family member. The records are also entered into a password-protected database. The information is used to learn more about the patient and their family history, track the patient’s medical care, and is also used for research purposes.

»What about confidentiality?

All records obtained by the Registry are kept in secure confidential files within the Registry Office. The only people permitted to review those records are the Registry personnel and physician caring for those patients. The Registry is approved by the Institutional Review Board (IRB) at Cleveland Clinic and is bound by regulator guidelines to assure patient confidentiality.

»How do I get in touch to the Registry?

The David G. Jagelman Inherited Colorectal Cancer Registry
Colorectal Surgery - A30
Cleveland Clinic
9500 Euclid Avenue
Cleveland, OH 44195
Telephone: 216.444.6470, 800.223.2273 ext. 46470

Polyposis Syndromes

Familial adenomatous polyposis»

Familial adenomatous polyposis (FAP) is a rare, hereditary syndrome characterized by multiple adenomatous polyps in the colorectum. FAP occurs in 1 in 10,000 people. The known genetic cause is mutations (genetic changes) in the APC gene. Individuals with FAP require lifelong gastrointestinal examinations and medical care by a health care team knowledgeable about FAP. This team may include gastroenterologists, colorectal and general surgeons, endocrinology specialists, primary care physicians, geneticists, genetic counselors, and oncologists. Individuals and families with FAP may find great benefit by joining a hereditary colon cancer registry.

Below you will find answers to the questions most frequently asked by individuals with FAP and their family members.

What is FAP?

FAP is a condition where control of cell growth is lost because a key gene that regulates cell growth is mutated. The main organ affected in FAP is the large intestine (colon and rectum). Here, individuals develop precancerous polyps called adenomas. Because patients who are born with an APC mutation have the mutation in every cell in their body they develop hundreds and even thousands of these potentially precancerous adenomas. Polyps generally start to grow at puberty and without treatment one or more adenomas will inevitably become cancer, at an average age of 39 years. Some people with have an ‘attenuated’ form of FAP and will develop less than a hundred adenomas in the colon, typically beginning in the late teens or early 20s.

About 90% of patients with FAP will also have polyps in the stomach. These polyps rarely cause any medical problems and are called fundic gland polyps. Nearly half of the time, the fundic gland polyps have dysplasia. Nearly 100% of patient with FAP will develop polyps in the duodenum (first part of the small bowel). Duodenal cancer may develop from duodenal polyps in a small percentage of patients. Patients with FAP may also develop thyroid cancer or other thyroid disease more commonly than the general population.

Individuals with FAP are at increased risk to develop other types of tumors. Benign tumors or growths such as osteomas in the bones, abnormal dental findings or soft tissue nodules under the skin, which often do not cause major health concerns.

While FAP is due to a genetic change in the APC gene, collections of findings outside of the intestinal tract are sometimes given different names. Gardner syndrome is often used when FAP occurs in someone with osteomas and soft tissue tumors. Turcot’s syndrome is used when FAP occurs with brain tumors.

What Are The Cancer Risks Associated With FAP?

FAP is associated with up to a 100% lifetime risk of colorectal cancer. The chance of developing colorectal cancer increases with age, with the average age of diagnosis at age 39 years.

Other cancers that can occur as part of FAP include duodenal, thyroid, small intestine, pancreatic, hepatoblastoma (liver cancer in childhood), medulloblastoma (brain tumor), gastric (stomach), small bowel, bile duct, and adrenal gland. The lifetime risk for each of these cancers is less than 2%.

Are There Any Other Risks Associated with FAP?

Other manifestations FAP can be seen in the bones (osteomas, usually affecting the skull and jaw), in the teeth ( unerupted teeth, supernumerary teeth, and odontomas); in the retinas of the eyes (congenital hypertrophy of the retinal pigment epithelium or CHRPE: pigmented lesions on the retinas that typically do not interfere with vision); in the soft tissue (tumors such as epidermoid cysts and fibromas on the skin), and in fibrous tissue (desmoid tumors).

Desmoid disease deserves a special mention because it is the second most common cause of death in patients with FAP, and causes major challenges for patients and doctors alike. Sporadic (not associated with FAP) desmoid tumors occur rarely in the general population but act somewhat like FAP desmoids. About 1/3rd of FAP patients will develop desmoid disease: half will get desmoid tumors and half will get desmoid sheets that grow on the mesentery (a sheet of tissue carrying blood vessels, nerves and lymph vessels to and from the bowel) of the small intestine and cause a puckering and distortion of the bowel that can lead to an obstruction. Desmoid tumors can grow inside the abdomen (50%), in the abdominal wall (45%) or outside the abdomen altogether (5%). When inside the abdomen they tend to grow around the arteries to the bowl, making surgical removal difficult or impossible, unless a lot of bowel is also removed. Even after removal, desmoids tend to come back.

The risk of desmoids varies between patients with FAP. Risk factors include a family history of desmoids, being a woman, having Gardner’s Syndrome and having an APC mutation beyond codon 1400. Because 80% of FAP-associated desmoids develop within 3 years of an abdominal surgery, we try to delay or avoid surgery in patients at high risk of desmoids. Laparoscopic surgery, by minimizing trauma, can also reduce desmoid risk.

When desmoids are diagnosed we give them a stage depending on their size, the symptoms they are causing, and the rate at which they grow. Stage I desmoids usually need no treatment, or just sulindac, an anti-inflammatory drug like motrin. Stage II desmoids are usually treated, either with sulindac alone or in combination with an estrogen blocking drug like raloxifene (Evista). Stage III desmoids need a mild chemotherapy, and stage IV desmoids need extreme chemotherapy. We also remove desmoids that are suitable for surgery, and operate on patients with desmoid complications such as bowel obstruction and fistula. Our surgery results are among the best ever published.

Overall, most patients with desmoid disease can live with it and are not very troubled. It gets milder as patients get older. In about 12% of patients the desmoids disappear all by themselves. In 7% of patients with desmoids, the disease is lethal, despite all out best care. The Sanford R. Weiss MD Center for Hereditary Colorectal Neoplasia has the most experience with FAP-associated desmoid disease in the country.

How is FAP Diagnosed?

The diagnosis of FAP is considered when multiple adenomatous polyps are found in the gastrointestinal tract.

Genetic counseling and genetic testing should be offered to anyone with numerous adenomatous polyps. Mutations in the gene APC have been associated with FAP. Genetic testing, which involves a blood draw or obtaining a brushing from the inside of the mouth (buccal swab), can be done to determine if an APC mutation is present. Once a mutation is identified in an individual, his or her family members can be tested for that mutation.

How is FAP Inherited?

Approximately 75% of individuals with FAP have a parent with the syndrome and the other 25% are the first in the family with the condition. FAP is inherited in an autosomal dominant manner. Everyone has two copies of the APC gene. Individuals with FAP have a mutation in one copy of the APC gene. The copy of the gene with the mutation can be passed on to future generations. The chance that a child of someone with FAP would inherit the copy of the gene with the mutation is 50%. The chance that he or she would not inherit the mutation is 50%.

Individuals diagnosed with FAP should inform their family members about their diagnosis and encourage them to undergo genetic counseling. This evaluation includes assessment of their personal history, exploration of the family history, and genetic testing for the APC gene mutation identified in the family. Recommendations to keep the patient and his or her family healthy and to prevent cancer will also be provided.

How is FAP Treated?

Currently, there is no cure for FAP. Because FAP cannot be cured, our aim is to prevent cancer at the same time as preserving a healthy, unaffected lifestyle for our patients. Patients should undergo lifelong examinations of the gastrointestinal tract and other at risk organs like the thyroid. Children with or at risk for FAP should begin having their colon checked if they get colon symptoms (bleeding in the bowel movements, abdominal pain, diarrhea) or yearly at puberty (10 to 12 years old), whichever is earlier. Surgery is the standard treatment to prevent colorectal cancer in FAP. The timing and choice of colon surgery depends on several factors, primarily the number and size of the polyps. If the colon polyp burden is mild, surgery may not be recommended till later in life. If there are too many polyps or other concerning polyp features like large size or advanced under the microscope, most patients will have their colon, or colon and rectum removed. This is usually done in the late teens or early twenties. The bowel is reconstructed by an ileorectal anastomosis (IRA) or a J pouch, so a permanent stoma (bag) is usually avoided. Laparoscopic surgery has made removal of the colon a lot less painful and a lot less disabling. The large intestine is checked yearly until surgery. Even after surgery the remaining bowel is checked yearly.

Since adenomatous polyps can develop in the duodenum, an upper endoscopy with biopsy of the papilla should be done beginning around the age of 20, every 1-3 years depending on the number, size, and microscopic analysis of the duodenal polyps. When the polyp burden is too great in the duodenum, surgery to prevent duodenal cancer may be recommended. The duodenum is removed and the intestinal tract is reconnected internally.

The thyroid is checked yearly by an ultrasound scan at the time of diagnosis or in the mid-teens years, whichever is earlier. Abnormalities such as cysts or calcifications are usually sampled at the time of ultrasound.

Where Can I Find More Information?

MYH-associated polyposis»

MYH-associated polyposis (MAP) is a rare, hereditary condition characterized by multiple adenomatous polyps in the colorectum. The known genetic cause is mutations (genetic changes) in the MYH gene. Individuals with MAP require lifelong gastrointestinal examinations and medical care by a health care team knowledgeable about MAP. This team may include gastroenterologists, surgeons, endocrinologists, primary care physicians, geneticists, genetic counselors, and oncologists. Individuals and families with MAP may find great benefit by joining a hereditary colon cancer registry.

Below you will find answers to the questions most frequently asked by individuals with MAP and their family members

What is MAP?

MYH is a gene involved in the repair of oxidative damage to the DNA. Oxidation causes changes in the DNA molecule that in turn affect many genes, including some genes responsible for regulation of cellular growth (such as the APC and KRAS genes). People with problems in the MYH gene can develop lots of different types of polyps in the large intestine, including adenomas, sessile serrated polyps and hyperplasic polyps. Most individuals with MAP usually develop between 10-100 polyps, although there have been some individuals with over 1,000 polyps. These polyps are often found in the late 40s. Individuals with MAP usually have fewer polyps than people with familial adenomatous polyposis (FAP). Because FAP and MAP appear similar, a detailed family history is important to help distinguish the two. MAP is different from other hereditary colorectal cancer syndromes because it is inherited in a recessive manner.

What Are The Cancer Risks Associated With MAP?

People with MAP are at an increased risk of developing colon and rectal cancer. The majority of colon cancers will occur between the fifth and seventh decade of life. An estimated 50% of people with MAP will have colorectal cancer at the time of diagnosis.

Are There Any Other Risks Associated With MAP?

Although MAP primarily affects the large intestine (colon) and rectum, the mutation is in every cell in the body and other organs can be affected. Patients can develop gastric fundic gland polyps (polyps in the stomach) and duodenal adenomas (polyps in the first part the small intestine); this risk is 4-25%. The fundic gland polyps are usually not pre-cancerous but the duodenal polyps, called adenomas, are pre-cancerous and may lead to duodenal cancer.

Based on some recent research, individuals with MAP are at an increased risk for developing thyroid disease or nodules on their thyroid that could develop into cancer. It is also suspected there is an increased risk to develop cancer of the kidneys.

How is MAP Diagnosed?

The diagnosis of MAP is suspected when multiple adenomatous polyps are found in the colon and rectum. MAP is suspected when an individual has greater than ten adenomatous colon or rectal polyps and does not have a mutation in the APC gene associated with FAP. MAP can also be considered if an individual has brothers or sisters with multiple colon polyps, but has no history of colon polyps or cancer in his or her parents.

Genetic counseling and genetic testing should be offered to anyone with a history described above. The gene MYH has been associated with MAP. Genetic testing, which involves a blood draw or obtaining a brushing from the inside of the mouth (buccal swab), can be done to determine if MYH mutations are present. MAP is diagnosed when a person is found to have two MYH gene mutations. In White individuals, the two most common mutations are Y165C and G382D. Once mutations are identified in an individual, his or her family members can be tested for that mutation.

How is MAP Inherited?

MAP is the only known syndrome of inherited colorectal cancer that is inherited in an autosomal recessive pattern. In recessive inheritance, both copies of the gene must be mutated for the disease to appear. Everyone has two copies of the MYH gene. Individuals with MAP have a mutation in each copy of the MYH gene. This means the mother and father of an individual with MAP each have one copy of the MYH with a mutation and are known as “carriers”. Carriers are not believed to have an increased risk of colorectal cancer or polyps. Approximately 1-2% of the population carries an MYH gene mutation.

The children of two mutation carriers have a 1 in 4 (25%) chance of having no MYH mutations. This person would be completely unaffected and could not pass any MYH mutations on to their children. There is a 2 in 4 (50%) chance of also being a carrier. These children would not MAP, but would have a chance of passing the one MYH mutation they have onto their own kids. Finally, there is a 1 in 4 (25%) of both MYH mutations being passed on, in which case this person would have MAP. All children of someone with MAP will have at least one MYH mutation.

Individuals diagnosed with MAP should inform their family members about their diagnosis and encourage their family members to undergo genetic counseling. This evaluation includes an evaluation of their personal history, exploration of the family history, and genetic testing for the MYH gene mutations identified in the family. Recommendations to keep the patient and his or her family healthy and to prevent cancer will also be provided.

How is MAP Treated?

Individuals with MAP are best monitored with colonoscopy starting at age 20 or 10 years prior the youngest diagnosis in the family, whichever is earlier. It is important that people with MAP have lifelong colonoscopies because new polyps can form that may turn into a cancer. If less than 20 polyps are found, they can be removed individually during a colonoscopy. If the polyps are too numerous or too fast growing, then surgical removal of the colon and/or rectum might be necessary. While the prospect of surgery may be upsetting, it is important to realize that without it, the risk of colorectal cancer is very high. The bowel is reconstructed by an ileorectal anastomosis (IRA) or a J pouch, so a permanent stoma (bag) is usually avoided.

The timing and choice of colon surgery depend on several factors, primarily the number and size of the polyps. Because MAP cannot be cured our aim is to prevent cancer but at the same time preserve a healthy, unaffected lifestyle for our patients. Laparoscopic surgery has made removal of the colon a lot less painful and a lot less disabling. Then the large intestine is checked yearly until surgery. Even after surgery the remaining bowel is checked yearly.

Certain non-steroidal, anti-inflammatory medications, such as sulindac have been shown to reduce, and may prevent, adenomatous colorectal polyps and can be considered for use in patient with MAP. The use of medications to prevent disease is called chemoprevention.

An upper endoscopy or an esophagogastroduodenoscopy (EGD) is also recommended beginning at age 20 and continue every 1-3 years, depending on the size, number and microscopic analysis of the duodenal polyp. All MAP patients should have a baseline thyroid ultrasound starting at the age of 20. This should be repeated yearly, or more frequently id abnormalities are detected.

Where Can I Find More Information?

Serrated polyposis syndrome/hyperplastic polyposis syndrome»

Serrated polyposis syndrome (SPS), also formerly called hyperplastic polyposis syndrome, is a condition that is characterized by serrated polyps in the colon and/or rectum. Serrated polyps are a type of growth that are defined by their saw tooth, or serrated appearance under the microscope. They can often be difficult to distinguish from other types of polyps in the colon and the only way to determine the type of polyp is by removing them and examining them under a microscope. There are different types of serrated polyps including hyperplastic polyps, sessile serrated polyps, and serrated adenomas. SPS is defined and diagnosed by the certain criteria defined by the World Health Organization. People with SPS have an increased risk of developing colorectal cancer and should undergo colonoscopy every year once a diagnosis is made.

How is SPS diagnosed?

SPS is a condition that is defined by the World Health Organization based on findings during endoscopic evaluation of the colon and rectum and confirmed with pathological examination of the polyps seen during colonoscopy. A patient meeting any one of the following criteria is diagnosed with SPS:

  1. The presence of 20 or more serrated polyps located anywhere in the colon
  2. The presence of 5 or more serrated polyps proximal to the splenic flexure, at least 2 equal to or greater than 1 cm in size
  3. The presence of any serrated polyp in the colon in a patient with a family history of SPS

What causes SPS?

SPS results from a tendency to develop serrated polyps in the colon and/or rectum. The exact cause is unknown. Although SPS is believed to be hereditary, no genetic defect has been identified to cause SPS. This means that there is no genetic test that can diagnose SPS.

What are the cancer risks associated with SPS?

People with SPS have an increased risk of developing colorectal cancer. About 25-40% of people with SPS will develop colorectal cancer. There are not any other cancer risks that have definitively been established to be associated with SPS and screening of other organs is not recommended.

What are the symptoms of SPS?

Symptoms are generally caused by the polyps or cancer that develop and are not specific to serrated polyps or to SPS. Common symptoms include bleeding, pain, diarrhea, or constipation. Patients may not have any symptoms. If you have any of the above symptoms, you should be evaluated by a physician.

Is my family at risk for getting SPS?

Various studies have suggested that SPS can be inherited, but the inheritance pattern is unknown. Therefore, it is advised that first-degree relatives (i.e., parents, siblings and children) of someone with SPS have an increased risk of developing SPS also.

How is SPS treated?

There is no cure for SPS. The treatment is directed at curing symptoms and removing polyps or cancers that are caused by SPS. This entails undergoing a yearly colonoscopy with removal of the polyps. If the polyps cannot be safely or completely removed, or if a cancer is found, surgery is recommended. The usual approach to a colon cancer is to remove the entire colon and reconnect the small bowel to the rectum. The entire colon and rectum is at risk to developing these polyps and cancer and thus any remaining colon or rectum still needs to be evaluated by endoscopy every year.

Where Can I Find More Information?

  • Rex DK, Ahnen DJ, Baron JA, Batts KP, Burke CA, et al. Serrated Lesions of the Colorectum: Review and Recommendations From and Expert Panel. Am J Gastroenterol. 2012 Jun 19. doi: 10.1038/ajg.2012.161. [Epub ahead of print];PMID: 22710576
  • Burke CA, Snover DC.Sessile serrated adenomas and their pit patterns: we must first see the forest through the trees. Am J Gastroenterol. 2012 Mar;107(3):470-2. PMID: 22388025
  • Vu HT, Lopez R, Bennett A, Burke CA. Individuals with sessile serrated polyps express an aggressive colorectal phenotype. Dis Colon Rectum. 2011;54(10):1216-23. PMID: 21904135

Juvenile polyposis syndrome»

Juvenile polyposis syndrome (JPS) is a rare, hereditary condition characterized by multiple juvenile polyps throughout the gastrointestinal tract. JPS occurs in 1 in 100,000 to 1 in 160,000 people. The known genetic causes are mutations (genetic changes) in the SMAD4 and BMPR1A genes. Individuals with JPS require lifelong gastrointestinal examinations and medical care by a health care team knowledgeable about JPS. This team may include gastroenterologists, surgeons, primary care physicians, geneticists, genetic counselors, and oncologists. Individuals and families with JPS may find great benefit by joining a hereditary colon cancer registry.

Below you will find answers to the questions most frequently asked by individuals with JPS and their family members.

What is JPS?

JPS is characterized by the presence of multiple juvenile polyps throughout the gastrointestinal tract. The term “juvenile” refers to the pathology (microscopic description) of the polyp rather than the age of the patient at the onset of the condition. Polyps are growths projecting from the intestinal lining, and juvenile polyps are a type of hamartomatous polyp (hamartomas are benign overgrowths of tissues normally present where the polyps grow), although sometimes juvenile polyps appear microscopically as inflammatory polyps. Juvenile polyps are most frequent in the colon, rectum and stomach but may also be present, rarely, in the small intestine. An individual with JPS may develop as few as five or as many as hundreds of polyps throughout his or her lifetime. Typically, the onset of polyps occurs in the teenage years. Secondary problems can develop from these polyps such as gastrointestinal bleeding, anemia, obstruction, unexplained weight loss, or the development of cancer.

What Are The Cancer Risks Associated With JPS?

Individuals with JPS are at increased risk to develop cancer in the gastrointestinal tract. The risk of developing cancer ranges from 9 to 68% over a lifetime. The most common site where cancer occurs is in the colon. Patients with JPS are also at risk for stomach and, rarely, small bowel cancer.

Are There Any Other Risks Associated with JPS?

Certain birth defects, such as cleft lip or palate, mal-rotations (abnormal placement of the internal organs), and heart defects have been described in 11-20% of individuals with JPS.

Individuals with SMAD4 gene changes are also at high risk to have a condition known as hereditary hemorrhagic telangiectasia (HHT). HHT is characterized by abnormalities in blood vessels, which cause arterial vessels to connect directly into veins instead of through capillaries. This can cause an abnormal collection of blood vessels (also known as arterial venous malformations) that can cause telangiectasias (red markings on the skin), nosebleeds, and hemorrhage (bleeding) in the brain, liver, lungs and other vital organs.

How is JPS Diagnosed?

The diagnosis of JPS is considered when multiple juvenile polyps are found in the gastrointestinal tract. While as many as 2% of children and some adults can have a single juvenile polyp, having only one juvenile polyp is not associated with JPS.

The diagnosis of JPS is made when the following is found:

  • More than five juvenile polyps in the colon and or rectum; or
  • Multiple juvenile polyps throughout the gastrointestinal tract; or
  • Any number of juvenile polyps in a patient with a family history of JPS.

Genetic counseling and genetic testing should be offered to anyone that meets these criteria. Two genes, SMAD4 and BMPR1A, have been associated with JPS. Genetic testing is done through a blood sample. Only 50% of individuals will have a mutation detected in either SMAD4 or BMPR1A. This means there are other genetic causes of JPS that are yet to be discovered. Once a mutation is identified in an individual, his or her family members can be tested for that mutation.

How is JPS Inherited?

Approximately 50% of individuals with JPS have a parent with the syndrome and the other 50% are the first in the family with the syndrome. JPS is inherited in an autosomal dominant manner. Everyone has two copies of the SMAD4 and BMPR1A genes. Individuals with JPS have a mutation in one copy of the SMAD4M gene or the BMPR1A gene. The copy of the gene with the mutation can be passed on to future generations. The chance that a child of someone with JPS would inherit the copy of the gene with the mutation is 50%. The chance that he or she would not inherit the mutation is 50%.

Individuals diagnosed with JPS should inform their family members about their diagnosis and encourage their family members to undergo genetic counseling. This includes an evaluation of their personal history, exploration of the family history, and genetic testing for the JPS gene mutation identified in the family. Recommendations to keep the patient and his or her family healthy and to prevent cancer will also be provided.

How is JPS Treated?

Currently, there is no cure for JPS. Patients should undergo lifelong examinations of the gastrointestinal tract to check for juvenile polyps and remove polyps when needed. This includes:

  • Colonoscopy beginning in the early teenage years or when symptoms develop, whichever occurs earlier. This should be repeated every one to three years depending on the number, size and pathology of polyps found
  • Upper endoscopy beginning in the mid twenties. This should be repeated every one to three years depending on the number, size, and pathology of the polyps found

Individuals with JPS are managed by removing polyps until the polyps become too numerous or large, cause symptoms, or advanced microscopically along the pathway toward cancer. When this happens in the colon, the colon is removed surgically. Occasionally it becomes necessary to surgically remove the stomach.

Surveillance for HHT should also be considered in individuals with SMAD4 gene mutations. This includes:

  • MRI of the brain using specialized protocols to check for vascular malformations in the brain, preferably in the first year of life, or at the time of JPS diagnosis, whichever is earlier
    • After an initial normal study no repeat MRI is recommended
  • Transthoracic contrast echocardiography (ultrasound of the heart) to screen for vascular malformations of the lung, preferably in the first year of life, or at the time of JPS diagnosis, whichever is earlier
    • If the initial test is normal, repeat screening should be considered after puberty, after pregnancy, within 2-years preceding planned pregnancy, and every 5-years thereafter
    • If the test is positive, CT scans of the lungs should be done to confirm the findings on echocardiography
  • Annual hemoglobin or hematocrit levels measurements in all patients over 35 years because of increased risk of gastrointestinal arteriovenous malformations
  • Ultrasound examination of the liver, to screen for vascular malformations, can be considered

Where Can I Find More Information?

Acknowledgement of her contribution
(Meghan Thompson, Shaker Heights High School, June 2007)


Peutz-Jeghers syndrome »

Peutz-Jeghers syndrome (PJS) is a rare, hereditary condition characterized by multiple polyps throughout the gastrointestinal tract and dark colored spots around the lips, mouth, hands and feet. PJS is also associated with an increased risk of cancer, particularly in the digestive tract and reproductive organs. PJS occurs in 1 in 250,000 to 280,000 people and is caused by changes (mutations) in the STK11/LKB1 gene. Individuals with PJS require lifelong gastrointestinal examinations and medical care by a health care team knowledgeable about PJS. This team may include gastroenterologists, surgeons, gynecologists, breast health specialists, primary care physicians, geneticists, genetic counselors, and oncologists. Individuals and families with PJS may find great benefit by joining a hereditary colon cancer registry.

Below you will find answers to the questions most frequently asked by individuals with PJS and their family members.

What is PJS?

PJS is characterized by the presence of multiple polyps throughout the gastrointestinal tract. Individuals with PJS develop Peutz-Jeghers polyps, which are a type of hamartomatous polyp. Hamartomas are benign overgrowths of tissues normally found at the place they grow. In PJS the polyps are most frequent in the small bowel, colon, stomach, and rectum. Some patients may develop polyps in the bladder, lungs, or nose. Occasionally, secondary problems can develop from the polyps in the digestive tract such as small bowel obstruction, gastrointestinal bleeding, anemia, stomach pain, or intussusception of the small bowel (in-folding of the small bowel into another section of bowel, drawn in by a polyp). These problems typically occur in very young patients, at puberty or in their early teen age years. Up to 50% of patients have experienced a small bowel obstruction requiring surgery, before their 20s.

Individuals with PJS can also develop dark colored spots (also called muco-cutaneous pigmentation) around or inside the mouth, around the eyes, nostrils, or anus, or on the hands and feet. Typically, these spots are dark brownish or bluish in childhood and fade in the late teenage years.

What Are The Cancer Risks Associated With PJS?

Individuals with PJS are at increased risk to develop cancer in the digestive tract and in certain reproductive organs. The lifetime risk of developing any sort of cancer is estimated to be as high as 93%. Men and women with PJS have a 39% risk of colon cancer, a 36% risk of developing pancreatic cancer, and a 29% risk of developing stomach cancer. Women have as high as a 54% lifetime risk of developing breast cancer. Also, rare tumors of the reproductive organs have been reported in PJS. Females can develop sex-cord tumors of the ovary and adenoma malignum of the cervix. These tumors can cause irregular periods or early puberty. Males can develop tumors of the sex-cord and Sertoli-cell type of the testicles. These tumors can cause male breast development and early puberty. Men and women also have a slightly increased risk of developing lung cancer.

How is PJS Diagnosed?

A diagnosis of PJS is considered in anyone with:

  • Three or more Peutz-Jeghers polyps; or
  • Any number of Peutz-Jeghers polyps with a family history of PJS; or
  • Characteristic dark colored spots with a family history of PJS; or
  • Any number of Peutz-Jeghers polyps and characteristic dark colored spots

Genetic counseling and genetic testing should be offered to anyone that meets these criteria. Genetic testing is done through a blood sample. Nearly all patients with PJS will have a mutation in STK11/LKB1. Once a mutation is identified in a patient, his or her family members can be tested for that mutation. Anyone found to have a mutation in STK11/LKB1 has PJS.

How is PJS Inherited?

Approximately 50% of individuals with PJS have a parent with the syndrome and the other 50% are the first in the family with the syndrome. PJS is inherited in an autosomal dominant manner. Everyone has two copies of the STK11/LKB1 gene. Individuals with PJS have a mutation in one copy of the STK11/LKB1 gene. The copy of the gene with the mutation can be passed on to future generations. The chance that a child of someone with PJS would inherit the copy of the gene with the mutation is 50%. The chance that he or she would not inherit the mutation is 50%.

Individuals diagnosed with PJS should inform their family members about their diagnosis and encourage their family members to undergo genetic counseling. This evaluation includes an evaluation of their personal history, exploration of the family history, and genetic testing for the PJS gene mutation identified in the family. Recommendations to keep the patient and his or her family healthy and to prevent cancer will also be provided.

How is PJS Treated?

Currently, there is no cure for PJS. Patients undergo lifelong surveillance to monitor for cancer and prevent secondary problems from the polyps. Some studies show that patient who are under close surveillance may avoid the need for emergency surgery and do not develop cancer. Recommended surveillance includes:

Women and Men

  • Annual physical examinations from birth
  • Upper endoscopy and capsule endoscopy every 2-3 years beginning around age 8-10 years
  • Colonoscopy every 2-3 years beginning in the late teenage years
  • Upper endoscopic ultrasound every 1-2 years beginning between ages 20-25 years

Women Only

  • Monthly self breast exams beginning at age 18
  • Breast exams by a healthcare provider twice a year beginning between the ages of 20-25 years
  • Annual mammogram and breast MRI beginning between the ages of 20-25 years
  • Annual pelvic exams and Pap smear beginning at age 18
  • Annual transvaginal ultrasound and CA-125 blood tests beginning between the ages of 20-25 years

Men Only

  • Consideration of ultrasound and examination of the testes every 2 years from birth to age 12

Where Can I Find More Information?

PTEN Hamartoma Tumor Syndrome, Cowden Syndrome, and Bannayan-Riley-Ruvalcaba Syndrome»

PTEN Hamartoma Tumor syndrome (PHTS) is a diagnosis given to someone who has a change (mutation) in the PTEN gene. Many patients diagnosed with either Cowden syndrome or BRRS by their clinical manifestations will be found to have a PTEN mutation. While Cowden syndrome and BRRS were first thought to be completely separate conditions, we now understand that all patients with PTEN mutations (and thus PHTS diagnoses) face similar health risks. Patients with PHTS can develop characteristics associated with both Cowden syndrome and BRRS over their lifetime.

Patients with Cowden syndrome tends to present in adulthood and may result in both benign and cancerous growths, which commonly affect the breasts, uterus, thyroid, gastrointestinal tract, skin, and tongue and gums. A common finding in Cowden syndrome is a large head size (macrocephaly). Cowden syndrome occurs in an estimated 1 out of every 250,000 people. The diagnosis of Cowden syndrome is made when a patient has enough characteristics to meet specific criteria (see below).

BRRS tends to present in childhood. This syndrome is suspected in individuals with fatty tumors (lipomas) on the skin, developmental delays, a large head size (macrocephaly), hamartomatous polyps in the gastrointestinal tract, vascular malformations such as hemangiomas, and, for boys, freckling on the penis.

Much is known about the risks associated with PHTS and Cowden syndrome, but little is known about the cancer risks or appropriate cancer screening for patients with BRRS who do not have a PTEN gene change. Therefore, we have only included information about PHTS and Cowden syndrome below.

Individuals with PHTS/Cowden syndrome require lifelong cancer screening and medical care by a health care team knowledgeable about PHTS/Cowden syndrome. This team may include endocrinologists, gastroenterologists, surgeons, gynecologists, breast health specialists, primary care physicians, geneticists, genetic counselors, hematologists, and oncologists.

What are the Manifestations of PHTS/Cowden Syndrome?

PHTS/Cowden syndrome is a condition that causes multiple benign and cancerous growths in certain organs. The benign growths commonly affect the breasts, uterus, thyroid gastrointestinal tract, skin, tongue, gums, and neurologic system.

Women with PHTS/Cowden syndrome can develop benign growths of many different types in their breasts. Common findings include fibrocystic changes, fibroadenomas, papillomas, and atypical ductal hyperplasia. Women with PHTS/Cowden syndrome can also develop benign fibroid tumors of the uterus. Men and women with PHTS/Cowden syndrome can also develop benign thyroid growths such as a multinodular goiter and/or Hashimito’s thyroiditis, an autoimmune thyroid condition.

An estimated 90% of patients with PHTS/Cowden syndrome will develop gastrointestinal polyps. The number of polyps patients may develop ranges from one to innumerable. Polyps can occur in both the colorectum and the upper gastrointestinal tract. Every microscopic type of polyp has been reported to occur in patients with PHTS/Cowden syndrome, but the most common types are hamartomatous and hyperplastic polyps, which both have low potential to become cancer.

The characteristic skin findings of patients with PHTS/Cowden syndrome are papillomatous papules (benign, skin-colored, raised bumps), trichilemmomas (benign tumors derived from the lower part of the outer sheath of the hair root, most frequently found on the head), and lipomas (benign fatty growths). Many patients develop papillomas on their gums and/or tongue, giving them a ‘cobblestone’ appearance. Men with PHTS/Cowden syndrome can develop freckles on their penis. In addition, many individuals with PHTS/Cowden syndrome have acral and plantar keratoses (dark flat spots on their hands and feet) and some also have hemangiomas or vascular malformations. The skin findings are often present by the time a patient is in their late 20s.

Persons with PHTS/Cowden syndrome also tend to have a large head size (macrocephaly) and a head shape that is longer than wide (dolichocephaly). Patients are also at increased risk to develop Lhermitte-Duclos disease, a benign tumor of the cerebellum (the part of the brain that controls coordination of movement). Autism and developmental delay have also been observed at increased frequency in persons with PHTS/Cowden syndrome.

What Are The Cancer Risks Associated With PHTS/Cowden Syndrome?

Risk for certain cancers is increased for patients with PHTS/Cowden syndrome.

Cancer Type General population risk Lifetime Risk with PHTS Lifetime Risk with Cowden syndrome, negative PTEN testing
Breast (female) 12% ~85% (average age of diagnosis in 40s) 25-50%
Thyroid 1% 35% (average age of diagnosis in 30s/40s) ~10%
Endometrial (uterine) 2.6% 28% (average age of diagnosis in 40s/50s) Thought to be increased, but exact risk unknown
Renal cell (kidney) 1.6% 34% (average age of diagnosis in 50s) Possibly increased, exact risk unknown
Colon 5% 9% (average age of diagnosis in 40s) Possibly increased, exact risk unknown
Melanoma 2% 6% (average age of diagnosis in 40s) Possibly increased, exact risk unknown

How is PHTS/Cowden Syndrome Diagnosed?

PHTS is diagnosed when a change (mutation) is found in the PTEN gene. The International Cowden Consortium has developed criteria to establish a diagnosis of Cowden syndrome. Additionally, both the National Comprehensive Cancer Network and the Cleveland Clinic (www.lerner.ccf.org/gmi/ccscore/) have established genetic testing criteria for PHTS/Cowden syndrome. These criteria are updated frequently based on new research. A PHTS/Cowden syndrome evaluation by a genetics professional should be considered for individuals with adult-onset Lhermitte-Duclos disease, macrocephaly plus autism/developmental delay, numerous and mixed types of gastrointestinal polyps, or a combination of PHTS/Cowden syndrome features, such as thyroid and uterine cancers or breast and kidney cancers.

If a patient is found to meet clinical or testing criteria, testing of the PTEN gene may be offered. Genetic testing is done through a blood sample. Once a mutation is identified in a patient, his or her family members can be tested for that mutation in order to determine who else in the family has PHTS.

How is PHTS/Cowden Syndrome Inherited?

PHTS/Cowden syndrome is inherited in an autosomal dominant manner. Everyone has two copies of the PTEN gene. Individuals with PHTS have a mutation in one copy of their PTEN gene pair. The copy of the gene with the mutation can be passed on to future generations. The chance that a child of someone with PHTS would inherit the copy of the gene with the mutation is 50%. The chance that he or she would not inherit the mutation is also 50%.

Individuals diagnosed with PHTS/Cowden syndrome should inform their family members about their diagnosis and encourage their family members to undergo genetic counseling. For patients with Cowden syndrome who do not have a PTEN gene mutation, family members may need evaluation by a medical geneticist to determine if they also meet the clinical criteria for a diagnosis of Cowden syndrome. This evaluation includes an evaluation of their personal history, exploration of the family history, and genetic testing if a PTEN gene mutation has previously been identified in the family. Recommendations to keep the patient and his or her family healthy and to prevent cancer will also be provided.

How is PHTS/Cowden Syndrome Treated?

Currently, there is no cure for PHTS/Cowden syndrome. Patients undergo lifelong surveillance to monitor for benign and cancerous growths to help detect any problems at the earliest, most treatable point in time.

We recommend that individuals with PHTS/Cowden syndrome have specialized breast cancer screening. This should include breast self-examination every month beginning at age 18, breast examination by a doctor or nurse every 3-6 months beginning at age 20, and mammography/breast MRI once a year beginning at age 25 or 5-10 years earlier than the youngest breast cancer diagnosis in the family. There are men with PHTS/Cowden syndrome who have developed breast cancer. Although the risk is much lower than that for women, we would recommend that the men perform monthly breast self-examination.

Some women at increased risk for breast cancer consider prophylactic mastectomy (removal of the breasts to prevent cancer). This is a consideration especially for women whose breast tissue is so dense that their physicians do not feel comfortable with traditional breast cancer screening techniques, or for those who have had repeated breast biopsies. One study has shown that prophylactic mastectomy reduces the risk for breast cancer by 90% in high-risk women.

Individuals with PHTS/Cowden syndrome should also receive thyroid cancer screening. For persons with PTEN mutations we recommend a baseline thyroid ultrasound at the age of diagnosis with at least yearly follow-up thereafter by an endocrine specialist. For those who are PTEN negative we recommend baseline ultrasound at age 18; if thyroid ultrasound is normal follow-up can be done by physical examination of the thyroid with their primary care provider. Thyroid nodules are often seen on thyroid ultrasound because they are common in PHTS/Cowden syndrome, but an expert will be able to determine whether or not they require biopsy or other further investigation.

In persons who are PTEN positive we also recommend imaging of the kidneys every two years starting at age 40.

A baseline colonoscopy should be done at age 35 or 40 years (or 10 years younger than the earliest colorectal cancer diagnosis in the family), with follow-up dependent on the number and type of polyps found. Both upper gastrointestinal and colorectal polyps are very common in persons with PTEN mutations. Baseline upper endoscopy often is recommended to help establish or confirm the diagnosis and surveillance of the stomach and small bowel is based upon the findings of the baseline exam.

Yearly dermatologic examination is also recommended.

Women who are PTEN positive should also see a gynecologic oncologist to discuss what kind of screening for endometrial cancer should be performed. Transvaginal ultrasounds as well as endometrial biopsies are both options.

For those who are PTEN negative but have a clinical diagnosis of Cowden syndrome, it is not recommend that screening of other organs beyond that mentioned for breast and thyroid cancers, be routinely performed. However, it should be based on a person’s family and personal history . We also recommend that the patient’s healthcare providers be aware of their diagnosis and the possible increase in risk for these cancer types so that appropriate assessment may be performed if the patient has concerning symptoms.

There are no studies that prove that cancer screening is effective for individuals with PHTS/Cowden syndrome. The recommendations are based on the opinion of experts in the field of cancer genetics and PHTS/Cowden syndrome. As with most cancer screening, these recommendations will hopefully help to detect cancers at an earlier stage when they are more treatable, but they cannot prevent the cancer from occurring.

Where Can I Find More Information?

Nonpolyposis Syndromes

Lynch syndrome/HNPCC»

Lynch syndrome is an inherited condition that causes an increased risk of colorectal cancer and cancer in certain other organs. Lynch syndrome occurs in approximately 1 in 400 individuals. Lynch syndrome is caused by mutations (genetic changes) in the ‘DNA mismatch repair’ genes. Individuals with Lynch syndrome require lifelong cancer screening beginning in adulthood and medical care by a health care team knowledgeable about Lynch syndrome. This team may include gastroenterologists, surgeons, gynecologic oncologists, urologists, dermatologists, gynecologists, primary care physicians, geneticists, genetic counselors, and oncologists. Individuals and families with Lynch syndrome may find great benefit by joining a hereditary colon cancer registry.

Below you will find answers to the questions most frequently asked by individuals with Lynch syndrome and their family members.

What is Lynch Syndrome?

Lynch syndrome is an inherited condition that causes an increased risk for colorectal cancer and cancer in certain other organs. Sometimes Lynch syndrome is also referred to as hereditary non-polyposis colorectal cancer (HNPCC). HNPCC is defined as a family that meets the “Amsterdam criteria,” which are:

  1. At least three relatives with colorectal or other HNPCC-related cancers, with one person being a first-degree relative (parent, child, or sibling) of the other two;
  2. At least two generations should be affected;
  3. At least one colorectal cancer diagnosis before age 50;
  4. Familial adenomatous polyposis is excluded.

HNPCC is a clinical diagnosis and is based on meeting the criteria above. Lynch syndrome can only be diagnosed by genetic testing and/or certain tests (described below) that can be done on a cancer. Lynch syndrome is caused by a mutation (genetic change) in one of several different genes. The genes that have been associated with Lynch Syndrome are MLH1, MSH2, MSH6, PMS2, and EPCAM. These genes affect the “DNA mismatch repair pathway,” which is responsible for correcting damage to DNA, the molecule that makes up genes. When a DNA mismatch repair gene is altered, this repair may not occur properly and, if so, DNA damage that occurs naturally in other genes will remain uncorrected. If enough DNA damage occurs in cell, it can cause cancer.

Lynch syndrome and HNPCC have very similar cancer risks, and, for the sake of simplicity, we will only use the term Lynch syndrome in this summary.

What Are The Cancer Risks Associated With Lynch Syndrome?

Site General Population Risk Lynch Syndrome Risk
Colon and rectum 5.9% 40-80%
Uterus 2-3% 20-60%
Ovaries 1-2% 1-20%
Stomach < 1% 1-10%
Small bowel < 1% 1-2%
Hepatobiliary tract < 1% 1-2%
Brain < 1% 1-8%
Kidney/bladder/ureter < 1% 1-12%

Many of these cancers develop at a significantly younger age than we would typically expect to see in the general population. For example, the average age of colorectal cancer diagnosis in Lynch syndrome is age 45, compared to age 69 in the general population.

There are also other important characteristics that we know about the colorectal cancers that are caused by Lynch syndrome. For example, these cancers tend to be more common on the right side of colon and can develop much more quickly than in the general population (1-2 years versus 10 years in the general population). We also know that if someone with Lynch syndrome is diagnosed with one colorectal cancer, they have a significantly increased risk of developing a second colorectal cancer. This risk is approximately 15% within ten years after the original surgery, 40% within 20 years, and 60% after 30 years.

Some individuals with Lynch syndrome will have a form of the condition called Muir-Torre syndrome. Individuals with Muir-Torre syndrome are at risk to develop the cancers listed above as well as benign skin growths (sebaceous adenomas, keratoacanthomas) and skin cancers (sebaceous carcinoma).

Are There Any Other Colon Risks Associated with Lynch Syndrome?

Individuals with Lynch syndrome may develop a few colorectal polyps, called adenomas, in the colon or rectum. If these polyps are not removed they could develop into a cancer.

How is Lynch Syndrome Diagnosed?

Colon and uterine cancers from individuals with Lynch syndrome will usually show changes in areas of DNA called “microsatellites”. These changes are called microsatellite instability or MSI. Tumors that have microsatellite instability are called MSI-high. Those without microsatellite instability are called MSS (microsatellite stable). Approximately 90-95% of colorectal cancers (and many endometrial cancers) from individuals with Lynch syndrome are MSI-H, while only about 10-15% of colorectal cancers not caused by Lynch syndrome are MSI-H. Thus, MSI testing can be used as a screening test to determine whether or not a family is likely to have Lynch syndrome. If the tumor is MSS, it is less likely that the cancer in the family is due to Lynch syndrome. However, since about 5-10% of Lynch syndrome tumors do not show instability, a negative MSI test cannot completely rule out the possibility of a Lynch syndrome diagnosis.

There is a second type of screening test for Lynch syndrome called immunohistochemistry (IHC). IHC testing is a screening test done on the tumor that looks for the expression of Lynch syndrome gene products (proteins). Approximately 88% of individuals with Lynch syndrome will have an abnormal IHC result. If one or more of the proteins are missing in the tumor it suggests that there is a mutation in that gene, which could then be found through genetic testing.

Ideally, MSI and/or IHC testing should be done before genetic testing is ordered. However, there are occasions where MSI or IHC cannot be done, in which case genetic testing can be performed. It is recommended that genetic counseling is done before ordering genetic testing. Genetic testing, which involves a blood draw or obtaining a brushing from the inside of the mouth (buccal swab), may help to determine whether a MLH1, MSH2, MSH6, PMS2, or EPCAM gene mutation is present in the family.

If genetic testing reveals a mutation, this confirms the diagnosis of Lynch Syndrome. If a genetic mutation is found, it is then possible to test other members of the family for Lynch Syndrome as well. Any other members of the family who have a mutation would also be at an increased risk for cancers associated with Lynch Syndrome and would need to be managed accordingly. If no mutation is found, Lynch syndrome is not necessarily excluded. Your genetic counselor will discuss the implications of a negative genetic test in the context of your family and your tumors.

How is Lynch syndrome Inherited?

Lynch syndrome is inherited in an autosomal dominant manner. This means that if you inherent one mutated or non-working copy of the gene, you will develop Lynch syndrome. Everyone has two copies (one from your mother and one from your father) of each of the genes that can cause Lynch syndrome. Individuals with Lynch syndrome have a mutation in one copy of the one of the mismatch repair genes (MLH1, MSH2, MSH6, PMS2, EPCAM). The copy of the gene with the mutation can be passed on to future generations. The chance that a child of someone with Lynch syndrome would inherit the copy of the gene with the mutation is 50%. The chance that he or she would not inherit the mutation is 50%.

Individuals diagnosed with Lynch syndrome should inform their family members about their diagnosis and encourage their family members to undergo genetic counseling. This includes an evaluation of their personal history, exploration of the family history, and genetic testing for the Lynch syndrome gene mutation identified in the family. Recommendations to keep the patient and his or her family healthy and to prevent cancer will also be provided.

How is Lynch Syndrome Treated?

Currently, there is no cure for Lynch syndrome. Patients should undergo lifelong cancer screening beginning in adulthood. This includes:

  • Colonoscopy is recommended every year for individuals with Lynch syndrome, starting at age 20 with follow up every 1-2 years until age 40. After age 40, colonoscopies should be performed every year. If cancer is found, consideration should be given to removing the entire colon, but annual screening should continue for rectal cancer. Prophylactic (preventative) removal of the colon is sometimes considered in cases where screening with colonoscopy cannot be performed. Regular colonoscopy for individuals with Lynch syndrome has been proven to decrease the colorectal cancer risk by more than 50%.
  • Women who have Lynch syndrome should undergo endometrial and ovarian cancer screening. This includes annual transvaginal ultrasounds and a CA-125 blood test beginning at age 30. Unfortunately, screening for ovarian cancer screening has not been shown to be effective. Therefore, some women with Lynch syndrome consider having a total hysterectomy (removal of the uterus) with salpingo-oophorectomy (removal of both fallopian tubes and ovaries) to eliminate their risk for developing endometrial cancer and to reduce the risk for ovarian cancer. This should be considered after age 35 or once childbearing is complete, whichever is later.
  • There is also additional screening that could be considered for men and women with Lynch syndrome. To screen for stomach cancer, a baseline upper endoscopy (EGD) should be done at age 25 with follow up no less than every 3 years. To screen for skin cancer, a baseline dermatology exam should be done at the time of diagnosis with follow up every year. All patients should have a baseline urinanalysis at age 35 with follow up annually. For families with a history of urothelial (bladder, ureter, etc) cancer or a mutation in the MSH2 gene, an ultrasound of the urinary tract should be performed. The ultrasound should be repeated every 5 years. Finally, for families with a history of small bowel cancer, a baseline capsule endoscopy should be done at age 30 with follow up every 3 years.

These recommendations were developed by the members of the Cleveland Clinic Sanford R Weiss Center for Inherited Colorectal Neoplasia based on professional society/consensus guidelines and expert opinion.

Where Can I Find More Information?

Familial colorectal cancer»

Familial colorectal cancer type X»

High Risk Clinic

The staff of the Sanford R. Weiss M.D. Center for Hereditary Colorectal Neoplasia is dedicated to serving patients and families with hereditary colon cancer. To minimize the burdens that can be associated with coordinating medical appointments recommended for patients with hereditary colorectal cancer syndromes, we have created a number of high risk clinics. The high risk clinic is offered a few times a month, with the goal of coordinating all of your appointments related to hereditary colorectal cancer in one day.

Services:

The registry coordinators will assist you in scheduling appointments depending on your syndrome and needs. The high risk clinic is staffed by health care providers from a variety of departments. To learn more about our providers, please see the “Our Team” tab.

High-Risk Clinic Day:

A high-risk clinic day has been set aside for individuals and families with inherited colorectal cancer syndromes who need to see multiple specialists. The goal is to make screenings and appointments easier by assisting you to schedule all of your appointments on one day during times set aside especially for you. However, if the days set aside do not fit your schedule, we are more than willing to accommodate you at alternative times.

Here is an example of a schedule for a patient with Lynch syndrome being seen in the high risk clinic.

  • 8 a.m. – Consultation with gynecologic oncologist
  • 9:15 a.m. – Consultation with dermatology
  • 10:30 a.m. – Consultation with colorectal surgeon
  • 11 a.m. – Colonoscopy and upper endoscopy
  • Noon – Lab appointment for blood work

Here is an example of a schedule for a patient with familial adenomatous polyposis being seen in the high risk clinic.

  • 9 a.m. – Thyroid ultrasound
  • 10 a.m. – Consultation with colorectal surgeon
  • 10:30 a.m. – Consultation with genetic counselor
  • 11:30 a.m. – Flexible sigmoidoscopy

During your visit, a registry coordinator will also be available to provide you with assistance. Your healthcare providers will be informed about your assessment and the recommendations made by the specialists in The Weiss Center.

Preparation for your Appointment:

When you call to make your appointment, the registry coordinator will take a family and medical history. Depending on your schedule, you may require special instructions. For example, if you are scheduled for a colonoscopy you will be required clean out your colon. These instructions will be discussed with you at the time of making the appointment. You may be asked to bring copies of your medical records with you, or to sign a release prior to your visit so that we may obtain the necessary medical records.

What to bring with you:
  • Photo identification and insurance card
  • Support person (or driver if having a procedure)
    • We plan on reviewing information with you and although we are always here to answer your questions a support person can assist with remembering the information.
    • If you are having a procedure with sedation (colonoscopy/EGD) you will be required to have a responsible adult accompany you.
  • Medical records
    • Any medical records, including copies of lab results, surgical pathology results, upper endoscopy/colonoscopy procedures, surgeries, genetic testing results, a list of medications, and anything else you may feel is important.
  • Family history
    • A family history is very important in determining proper care and treatment for you. You can use the following file to make a record of your family history or you can write down a list of important information about your family members such as cancers (and age occurred), surgeries, polyps, children, names, ages, and any genetic testing.
Making an appointment

To make an appointment or to learn more about the David G. Jagelman, M.D. Registries and high risk clinic please contact one of our coordinators at: 216.444.6470 (polyposis), 216.444.4307 (HNPCC/Lynch syndrome) or toll free at 800.223.2273 extension 46470 or 44307.

Carol Burke, MD
Gastroenterologist
  • Dr. Burke is a doctor who specializes in diseases of the digestive tract; particularly she treats patients with or at risk for polyposis and hereditary colorectal cancer.
  • She determines the appropriate strategies to diagnose the cause of the condition and performs endoscopic examinations including EGD (upper and side viewing endoscopy), enteroscopy, and colonoscopy.
  • She also provides preventive services such as surveillance procedures in addition to prescribing chemoprevention (medications given to prevent or slow the development of polyps or cancer).
Steven Campbell, MD, PhD
Urologist
  • Dr. Campell is a surgeon who evaluates and treats diseases of the genitourinary tract (organs such as the ureter, bladder or kidneys).
  • He consults with patients in clinic, performs surgery, and coordinates screening for cancers of the bladder, ureter or kidneys by tests such as cystoscopy, urine studies, or urinary system CAT scans and/or ultrasound.
James Church, MD
Colorectal Surgeon
  • Dr. Church is a surgeon who is the Director of the Weiss Center and Jagelman Registries.
  • He specializes in the treatment and prevention of hereditary colorectal cancer and desmoids.
  • He consults with patients in clinic, and performs surgery, colonoscopies and sigmoidoscopies.
  • He has expertise in the management of patients with desmoids.
Charis Eng, MD, PhD
Geneticist
  • Dr. Eng is a medical geneticist.
  • She works with a genetic counselor to evaluate personal and family histories to determine if and what genetic testing is appropriate.
  • She coordinates genetic testing and helps patients better under the risk for them and their family members to develop cancer.
  • Dr. Eng also runs a research lab that studies PTEN-hamartoma tumor syndrome.
Hennie Hasson, RN
  • Hennie is a clinical research nurse who coordinates research studies done by Dr. Burke for patients with hereditary colon cancer syndromes.
Matthew Kalady, MD
Colorectal Surgeon
  • Dr. Kalady is a surgeon who specializes in diseases of the colon and rectum.
  • He specializes in hereditary colorectal cancer syndromes.
  • He consults with patients in clinic, performs sigmoidoscopies, and specializes in laparoscopic colorectal surgery for patients that require surgery.
Sara Kravochuck, RN, BSN
HNPCC/Lynch Syndrome Registry Coordinator
  • Sara is a coordinator for our non-polyposis registry.
  • She consents patients to the registry, coordinates medical appointments, collects and reviews medical records, enters information about patients into our database, and maintains long-term follow up with patients and their families.
Lisa LaGuardia, RN
Polyposis Registry Coordinator
  • Lisa is a coordinator for our polyposis registry.
  • She consents patients to the registry, coordinates medical appointments, collects and reviews medical records, enters information about patients into our database, and maintains long-term follow up with patients and their families.
Brandie Leach, MS
Genetic Counselor
  • Brandie sees patients with or at risk for hereditary colorectal cancer syndromes.
  • She evaluates personal and family histories to determine if and what genetic testing is appropriate.
  • She coordinates genetic testing and helps patients better under the risk for them and their family members to develop cancer.
Jessica Moline, MS
Genetic Counselor
  • Jessica sees patients with or at risk for hereditary colorectal cancer syndromes.
  • She evaluates personal and family histories to determine if and what genetic testing is appropriate.
  • She coordinates genetic testing and helps patients better under the risk for them and their family members to develop cancer.
Margaret O’Malley, BS
Polyposis Registry Coordinator
  • Margaret is a coordinator for our polyposis registry.
  • She consents patients to the registry, coordinates medical appointments, collects and reviews medical records, enters information about patients into our database, and maintains long-term follow up with patients and their families.
Joseph Parambil, MD
Pulmonologist
  • Dr. Parambil is a doctor who treats lung diseases.
  • He coordinates screening for and treatment of ateriovenous malformations (AVMs) identified in the lungs of patients with juvenile polyposis syndrome-hereditary hemorrhagic telangiectasia.
Holly Pederson, MD
Breast Specialist
  • Dr. Pederson is a doctor who evaluates patients with a high risk of developing breast cancer for reasons such as a genetic condition or a family history.
  • She sees patients in clinic and coordinates breast cancer screening by mammogram or breast MRI and physical examination.
Joyce Shin, MD
Endocrine Surgeon
  • Dr. Shin is a surgeon who specializes in treatment of endocrine diseases, especially of the thyroid.
  • Dr. Shin sees patients in clinic, does surgery, and coordinates screening for thyroid diseases and cancers by ultrasound, physical examination, and blood work.
Tyler Stevens, MD
Gastroenterologist
  • Dr. Stevens is a gastroenterologist who specializes in pancreatic diseases, including pancreatic cancer.
  • Dr. Stevens sees patients in clinic and does screening for pancreatic cancer with tests such as endoscopic ultrasound, MRI, and ERCP.
R. Matthew Walsh, MD
Surgeon
  • Dr. Walsh is a general surgeon who specializes in diseases and cancers of the upper gastrointestinal tract.
  • Some of the surgeries Dr. Walsh does for patients with hereditary colorectal cancer syndromes include gastrectomies (removal of the stomach) and duodenectomy (removal of the duodenum).
  • He also does procedures to screen the upper gastrointestinal tract, such as EGD.
Xhileta Xhaja, MD
Research Assistant
  • Xhileta is a research assistant who helps Dr.Church maintain the desmoid disease registry for patients with familial adenomatous polyposis who have developed a desmoid.

To schedule an appointment or learn more about our services, please call 216.444.6470 or toll free at 800.223.2273 ext. 46470

eConsult

Get a diagnosis without traveling to Cleveland. With our MyConsult Online Second Opinion service, following a thorough review of your medical records and diagnostic tests, our physician specialists render a second opinion that can be shared with your doctor.

Learn more

Schedule an Appointment Online

Call us for an Appointment

To find a digestive specialist for your needs, contact the Digestive Disease Institute at 216.444.7000 (or toll-free 1.800.223.2273, ext. 47000)

Same-day Appointments

To arrange a same-day visit, call 216.444.7000

This information is provided by Cleveland Clinic and is not intended to replace the medical advice of your doctor or health care provider. Please consult your health care provider for advice about a specific medical condition.

© Copyright 2014 Cleveland Clinic. All rights reserved.

Cleveland Clinic Mobile Site