Lynch Syndrome International

 

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Photo Courtesy of Bilal Kamoon

{slider=What is Lynch syndrome?}

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC) predisposes individuals to an approximate 80% chance of contracting colorectal cancer during one's lifetime as well as an up to 60% chance of contracting endometrial cancer.  Diagnosed individuals possess a higher than average risk of contracting various cancers of the gastrointestinal organs, cancers of the abdominal area, the ovaries, the esophaegus, the bladder, the ureter, the kidneys, the liver, the gallbladder duct, the pancreas, the prostate, the skin and the brain.

Because Lynch syndrome is hereditary, a 50% chance exists that a person will pass it down to one's children.  Lynch syndrome does not skip generations.

Lynch syndrome is the result of an inherited genetic defect mostly involving the MLH1, MSH2, MSH6 and PMS2 genes. Other less common mutated genes involved with Lynch syndrome exist, including the newly discovered MYH gene, associated with Muir Torre and sebaceous lesions. However the most common are the MLH1 and the MSH2.

 

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{slider=What is gene mutation?}

Gene mutations are basically a permanent change in the DNA.  DNA is active and always replicating itself.  If it makes a mistake, then a mutation occurs.

Gene mutations can be inherited or can develop in the sperm or in the egg (called de novo.)  These mutated genes can pass down through the generations. The particular genes of Lynch syndrome are called "mismatch repair genes."  They repair problems (mismatches) that occur during duplication of the genetic code when other genes are made.  If there is a defect in these genes, mismatches won't be repaired properly and cancer cells may develop.

Some gene mutations are a result of environmental factors (such as sun radiation, poor water, ingested foods with DNA altering qualities) and acquired during one's lifetime.  These mutations are not hereditary, however the interplay between the environment and the predisposition to cancers can exacerbate the development of Lynch cancers.

 

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{slider=How common is Lynch syndrome?}

In the general population, the prevalence of Lynch syndrome is predicted between 1-in-500 and 1-in-1,000.  To put this into perspective, It is projected there are approximately 600,000 mutation carriers within the U.S., however it is also projected only 5% of those individuals have been diagnosed, to date.

What we do know is for each individual diagnosed, there are between twenty and over one hundred other related persons who may also be affected and who benefits from that one diagnosis.  A failure to diagnose Lynch syndrome is a failure to diagnose an entire family.

 

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{slider=How is Lynch syndrome diagnosed?}

Lynch syndrome can only be accurately diagnosed through genetic testing.  There are many steps which lead up to this process including the documentation of a family history, shared with your medical provider and/or genetics counselor who will determine whether or not it appears you may be at high risk for Lynch syndrome.

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{slider=What is the difference between Lynch I and Lynch II?}

Lynch I solely refers to families in which colon cancer is the sole contracted cancer.  Lynch II families sustain a variety of cancers, such as endometrial, pelvic-renal, ovarian, etc., in addition to colon cancer.

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{slider=If I get diagnosed, is there a treatment for the cancers?}

Not all persons diagnosed with Lynch syndrome get cancer.   As well, many others develop polyps which are removed by colonoscopy or other intervention before they become cancerous. Besides protecting our children and generations to come, the benefit of diagnosis is the ability to obtain annual testing for cancer, called surveillance testing, which may be lifesaving. So, to answer the question, there is not only treatment through resection (removal of cancers and affected organs) chemotherapy and radiation, but there is also a system of annual testing, which if utilized correctly, growths are removed prior to becoming cancerous!

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{slider=Why does testing need to be completed annually?}

Most cancers take years for the tumors to grow. Lynch syndrome cancers are far more aggressive than other cancers and grow and metastasize very rapidly, often becoming cancerous and dangerous in as little as two years.  Early detection is essential for survival.

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{slider=Is there a cure?}

No.  Researchers have been working very hard to find one.  At Case Western University, Dr. Sanford Markowitz has a vision of finding a way to put the breaks on the mutated gene to counter the mutated gene's attempts to put on the gas!  There are dedicated researchers all over the world trying to figure out what can be done to control the mutation. In the meantime, the closest thing to a cure is genetic testing to determine the existence of the mutated gene and the level of risk.  With that knowledge, implementing annual surveillance testing provides a rate of insurance for early detection of cancer, at a time when it is most treatable and before it becomes a threat to survival.

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{slider=My mother has colon cancer and we think her mother had it, but aren't sure.....}

.......Is there a way we can find out if she  is at  high risk for Lynch syndrome, before proceeding directly toward genetic testing?

Yes. Your mother's tumor can be pathologically tested for certain qualities of Lynch syndrome.  Ask her doctor to refer it for MSI or IHC testing.  Many professional organizations and associations are calling for this testing of the tumor to become a standard of care any time colon cancer or endometrial cancer has been diagnosed.  If the family history indicates there may be a high risk of contracting cancer heritability, always ask for the tumor to be tested through MSI.  The testing is not all that expensive and it may be well worth the investment, if your family history indicates there may be a high risk for Lynch syndrome, for everyone to chip in together and pay for it if insurance doesn't cover the cost.

Remember, the MSI is not a conclusive test.  It is only a presumptive test that would need to be confirmed with genetic testing but it is a good, inexpensive start.

 

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{slider=How many cases of colon cancer in my family should cause concern?}

That depends upon the specifics of your family history.  But, if you have one person in your family with early onset colorectal cancer or with endometrial cancer, it is more than enough to prompt a visit to your physician to discuss Lynch syndrome!

 

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{slider=How serious is the risk of endometrial cancer?}

Endometrial cancer is the most common of women's cancers.  Annually, approximately 40,000 new cases are diagnosed and there are approximately 6,500 deaths.  Every woman has an approximate 2% risk of endometrial cancer however the woman with Lynch syndrome has an almost up to 65% risk of contracting it.  Those are pretty serious numbers. Today, we have put so much focus on "thinking pink" we have forgotten about all the other colors in the cancer rainbow--the dark blues, the teals and the peaches.  It is time to bring notice to the cancers that play dirty and "hit below the belt."

 

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{slider=How serious is the risk of colon cancer?}

Colorectal cancer is the second largest cause of cancer deaths in the U.S. Approximately 150,000 people will be diagnosed with it during 2010 and 60,000 will die.  However the survival rate for those with colon cancer found early is more than 90%.  Individuals with Lynch syndrome have an almost 80% lifetime risk of getting colon cancer.  Therefore, that early detection is important for survival and in order to get that, it is very important to be diagnosed through genetic testing.

 

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{slider=What about the skin cancers?}

Muir Torre syndrome is a variant of Lynch syndrome. It is a genetic syndrome characterized by a combination of sebaceous tumors (tumors of the oil glands in the skin) and one or more internal Lynch malignancies, most often colon cancer.  In the past year, there has been a call to action that all sebaceous tumors be tested through MRI (pathology testing) for Lynch syndrome.

 

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{slider=What is a "biallelic mutation" and how is it different?}

Known as "Turcot syndrome," "Lynch syndrome III and MMR-D syndrome, a biallelic mutation predisposes individuals to an increased risk of developing brain tumors, leukemia, lymphoma, small bowel cancer and colorectal cancer.  It is rare and fewer than seventy-five families in the United States are known to have it.  About 16% are first diagnosed with colorectal cancer and the other introductory cancers are brain cancer, leukemia or lymphoma, prior to development in the gastrointestinal tract.  Commonly recognized feature are numerous colon polyps, which often lead to a mistaken diagnosis of FAP. The average age for colorectal diagnosis is sixteen, however cancers have been diagnosed from infancy through middle adulthood.  A physical feature appearing to be common with this are dark spots on the skin called cafe au lait (CAL) spots.  It has been suggested that any child presenting with an early onset malignancy and cafe au lait spots should be tested for mismatch repair gene presentations. It is believed to occur when both parents have a mutated Lynch syndrome gene.

 

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Lynch Syndrome International invites the media to learn more about our organization and assist us in promoting public awareness of Lynch syndrome.  As the only national and international nonprofit organization to address the needs and concerns of those who are affected by the myriad of cancers associated with Lynch syndrome, we very much need you to help us in our mission to protect families and save lives.

Please feel free to peruse our site to learn more about Lynch Syndrome International and use our resources, including our LSI Library, in order to obtain valid up to date, sourced, information on Lynch syndrome.  In addition to the information listed upon the website, we can provide you with resources which may assist in adding a "local slant" being produced, including survivors and previvors who are available to interview and share their personal experiences with Lynch syndrome as well as contact information for experts in the field of Lynch syndrome.

We are always available by email at This email address is being protected from spambots. You need JavaScript enabled to view it. or by telephone at 707-689-5089.  We look forward to hearing from you. Together, we can make a postive difference in the lives of tens of thousands of people, within our communities throughout the world.

 

 

 

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Photo Courtesy of Marco Pompei

 

Medicine is not merely a science but an art. The character of the physician may act more powerfully upon the patient than the drugs employed.

-~ Paracelsus

For Professionals

Understanding the busy schedule of the professional, the following pages are quick guides for professionals to acquaint them with the basic knowledge of Lynch syndrome and how to diagnose and manage the disorder.

More detailed information to supplement these pages can be found by clicking on the LSI Library link on the Main Menu, to the left of this page, where selected studies are available as well as clinical trials, registries, patient payment assistance programs, anti-discrimination laws and other resources relative to Lynch syndrome.

Simply follow the links on the top right to review the basic steps providing information on the diagnosis of the Lynch syndrome.

 

 

Modified 5/18/2014

 


Photo Courtesy of the National Institute of Health

 

Characteristics of Lynch Syndrome

For those of us who have been diagnosed with cancer, time is a precious commodity. The time and distance from the scientist's lab bench to the patient's bedside must be shortened. ~ Larry Lucchino

 

Autosomal dominant inheritance pattern

Earlier average age of onset of colorectal cancer than in the general population (45 years in Lynch syndrome v. 63 years in the general population)

  • Proximal (right sided) colonic cancer predilection (70%-85% of colorectal cancers in Lynch syndrome are proximal to the splenic flexure)*

Accelerated carcinogenesis (tiny adenomas can develop carcinoma within 2-3 years in Lynch syndrome v. 8-10 years in the general population)

 

·        

 

 

 

MLH1-MSH2

1,2

MSH6

2

 

PMS2

3

Cancer

Gen Pop1

 

Risk

Avg Age

 

Risk

Avg Age

 

Risk

Avg Age

---------------

------------

 

-----------

-----

 

--------------

-----

 

----------

-----------

Colon

5.50%

 

40%-40%

44-81 yrs

 

10%-22%

54 yrs

 

15%-20%

51-66 yrs

Endometrium

2.70%

 

25%-60%

48-62 yrs

 

16%-28%

55 yrs

 

15%               

49 yrs

Stomach

<1%

 

1%-13%

56 yrs

 

<3%

63 yrs

 

6%*

70-73 yrs

Ovaries

1.60%

 

4%-24%

42.5 yrs

 

1%-11%

46 yrs

 

6%*

42 yrs

Hepatobiliary Tract

<1%

 

1.4%-4%

50-57 yrs

 

Unk

Unk

 

6%*

Unknown

Urinary Tract

<1%

 

1%-4%

54-60 yrs

 

1%               

65 yrs

 

6%*

Unknown

Small Bowel

<1%

 

3%-8%

47-49 yrs

 

Unk

54 yrs

 

6%*

59 yrs

Brain/CNS

<1%

 

1%-3%

50 yrs

 

Unk

Unk

 

6%*

45 yrs

Sebaceous Neoplasms

<1%

 

1%-9%

Unk

 

Unk

Unk

 

Unknown

Unknown

Pancreas4

<1%

 

1%-6%

Unk

 

1%-6%

Unk

 

Unknown

Unknown

 

 

1. Kohlman, W Gruber, SB

2012

 

www.genetests.org

 

1,2 Bonatel et al

Jama 2011

 

 

 

 

3 Sentel, et al

Gastroentrology 2008

 

 

4 Kastrinos et al

Jama 2009

 

 

 

 

* Starred Cancers combined = 6% Risk.

 

 

The Basics of Identification, Diagnosis and Management of Lynch Syndrome

Identification, Diagnosis and Management - Excellent Immediate Resource Guide for Physicians: Lynch Syndrome by Wendy Kohlman, MS and Stephen B. Gruber, MD, PhD, revised 9/20/2012

 

 

Other characteristics include:

 

  • Brain/CNS (1%-3% )

Sebaceous adenomas, sebaceous carcinomas and multiple keratoacanthomas in Muir-Torre syndrome (variant of Lynch syndrome)

Subset of Breast Cancer

  • Pathology of colorectal cancer is more often poorly differentiated, with an excess of mucoid and signet cell features, a Crohn-like reaction and an excess of infiltrating lymphocites within the tumor.

Increased survival from colorectal cancer

 

* In the MSH-6 mutation, most individuals have colorectal cancers located on the left side of the colon; including the descending colon, the sigmoid colon and the rectum, different from many of those with Lynch syndrome in which the cancers are proximal. There are more cases of endometrial cancer within those with an MSH-6 mutation.

 

Modified 5/18/2014

 


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Diagnostic Guidelines and Tools

 

DIAGNOSTIC GUIDELINES AND TOOLS

 

 ASSESSING FAMILY HISTORY FOR DIRECT REFERRAL FOR GENETIC SEQUENCE TESTING

 

NCCN Guidelines dramatically increased the guidelines for genetic testing of Lynch syndrome in 2014.  These changes include:

  1. The accepted use of diagnostic tools providing a quick resource to determine whether it is appropriate to prescribe genetic testing for patients who meet a five percent or greater risk threshold for Lynch syndrome have been approved by NCCN.  These include: 
  •          PREMM 1,2,6  (A very quick, 2 minute family history questionaire prediction tool to determine the clinical probability of an individual
  •          carrying a mutation of the basic Lynch cancers of MLH1, MSH2 and MSH6)
  •          MMR Pro - This assessment device developed by Johns Hopkins researchers allows medical health professionals and families to
  •          make decisions about cancer prevention screenings.  Requires download.
  •  
  •          Both tools calculates the risk of an indvidual carrying a gene defect and alleviates time necessary to assess family history and is stated
  •          to more accurately identify at risk individuals.  Download page and tool information.

2. A recommendation for panel testing for the five Lynch syndrome genes instead of sequential testing; and;

3. It acknowledged individuals with cancer may directly proceed to genetic testing without having to undergo a complicated and time intensive tissue screening algorithm.

 

 

"If you don't ask the right questions, you do not get the right answers. A question asked in the right way often points to its own answer. Asking questions is the A-B-C of diagnosis. Only the inquiring mind solves problems.

-Edward Hodnett (1841-1920)

 

Some insurance companies still insist upon the patient meeting the older standards of criteria.  It is important to ask the right questions. Most patients are not familiar with the organs of the body or medical terms determining where in the specific organ the cancer occurred.  However, they may recall some terminology, such as, "She had a whipple." or "I think it was between the kidneys and the bladder where it happened."  So, it is important to ask about age and the location of the tumors, trying to decipher where it could have occurred.  Most patients will stop the process of diagnosis if they are required to present their family's medical records.      

 

Amsterdam Criteria I for HNPCC

The following must be met in order to make a diagnosis of Lynch syndrome:

 

  • Three affected relatives with verified colorectal cancer
  • One is a first-degree relative of the other two
  • Two successive generations affected
  • One of the relatives with colorectal cancer diagnosed under age fifty
  • Familial Adenamomatus Polyposis (FAP) should be ruled out.

 

 

Amsterdam Criteria II for HNPCC

The following must be met in order to make a diagnosis of Lynch syndrome:

 

  • Three affected relatives with an HNPCC-associated cancer
  • One is a first-degree relative of the other two
  • Two successive generations affected
  • One of the relatives with HNPCC-associated cancer diagnosed under age fifty
  • Familial Adenamomatus Polyposis (FAP) should be ruled out.

 

Approximately 50% of those meeting the Amsterdam II criteria will have Lynch syndrome.

 

Assess family history and determine whether or not to refer to a genetic counselor or perform the test.  In some areas, it is taking up to ten months to obtain the services of a genetic counselor, however, some insurance companies will not pay for the genetic test unless genetic counseling services are provided.  Be sure and check with the insurance company to determine their policy.

Before taking the test, be sure and provide informed consent to the patient.  

Testing can be provided through most commercial laboratories.  Make certain the laboratory is able to provide a comprehensive test for each of the genes.  Some do not.  Finally, make sure the lab is CLIA approved and positive tests are run with a second blind test to confirm the results.Be sure and ask the current delay times in providing results.  Some labs are taking up to six to twelve weeks for results to be returned.

 

                                                                             MOLECULAR TESTING OF TUMORS

 

The second prong in determining whether or not the patient meets the criteria for diagnostic testing is molecular testing of all colorectal testing of tumors to determine if characteristics of Lynch syndrome exists.  This is commonly referred to by the genetics community as "universal testing."

LSI encourages all colorectal and endometrial cancer tumors be tested for characteristics of Lynch syndrome.  This does not provide a large number of diagnoses annually, however, may identify families which do not meet the family history criteria. This is important as only approximately 50% meet Amsterdam guideline criteria.  

Considering approximately 149,00 cases of colorectal cancer occur annually and 3% may be a result of Lynch syndrome, the maximum of only 4,470 persons tested as a result of colorectal cancer each year hardly puts a dent into the need to diagnose the approximate 700,000 persons in the U.S. alone, believed to be at risk for Lynch syndrome. The likely number of the effect of universal testing resulting in genetic testing is approximately fifty percent or 2,270 persons per year, which would result in approximately 11,350 diagnosed annually if four other family members would consent to genetic testing, as well.

Asking each patient their family history of cancer and aggressively molecularly testing each tumor will significantly reduce the above number of individuals yet to be diagnosed.  The answer and resolution of protecting families with hereditary cancers rests with our physicians to either test our families or refer those who meet the criteria for testing to genetic counselors.

Below is the Bethesda criteria to determine if this testing is necessary as a precursor test for genetic sequencing.  Some insurance companies may require it, so be certain to contact the insurance companies first for their guidelines and obtain approval for genetic testing prior to providing the test.  The input of a genetic counselor is beneficial when performing molecular testing.

 

 

Revised Bethesda Guidelines - testing of tumors for microsatellite instability (MSI)

Preliminary MSI testing of tumors should occur in the following situations:

  • Colorectal cancer diagnosed in individuals under the age of 50
  • Presence of synchronous, metachronous colorectal, or other HNPCC-associated tumors, regardless of age
  • Colorectal cancer with the MSI-H histology diagnosed in a patient <60 years of age
  • Colorectal cancer diagnosed in a patient with one or more first-degree relatives with an HNPCC-related tumor, one cancer being diagnosed
  • Colorectal cancer diagnosed in two or more first-degree or second-degree relatives with HNPCC-related tumors, regardless of age

 

† MSI-H = high microsatellite instability in tumors refers to changes in two or more of the five NCI-recommended panels of microsatellite markers. MSI-L = low microsatellite instability in tumors refers to changes in only one of the five NCI-recommended panels of microsatellite markers.

Hereditary Nonpolyposis Colorectal Cancer (HNPCC)-related tumors include colorectal, endometrial, stomach, ovarian, pancreas, bladder, ureter and renal pelvis, biliary tract, brain (usually glioblastoma as seen in Turcot Syndrome), prostate, sebaceous gland adenomas and keratoacanthomas in Muir-Torre syndrome, and carcinoma of the small bowel.

Breast cancer has been identified as an integral component of LS based upon mismatch repair germline mutation factors in breast cancer tissues from family members who are not only at high risk, but, moreover, who had Lynch syndrome cancers, such as involving the colorectum. Breast cancer is exceedingly common in the population and, therein, its occurence in Lynch syndrome families could be due to chance, but importantly, a subset will likely be integrally related to a germline mismatch repair Lynch syndrome mutation is some LS families. Therefore, it would be prudent to mount a screening and management program for Lynch syndrome in those families where breast cancer is believed to be an integral lesion.

 

Diagnostic Codes For Lynch Syndrome (Codes Are In The Process Of Change)

 

NCCN Guidelines Have Been Revised 2014 for Lynch Syndrome HNPCC Cancers  Sign Up and Log In

Revised European Guidelines June 2013

EGAPP Recommendations for Preliminary Screening And Genetic Testing

American Society of Breast Surgeon Guidelines

American Society of Clinical Oncologists Guidelines

ACMG Guidelines 9/17/2013

Society of Gynecological Oncologists Statement on Prophylactic Surgery

AMA Activity For Medical Professionals To Identify High Risk Individuals

National Society of Genetic Counselors

 

 

Reviewed 5/18/2014

 

 

 


 

Screening and Management

RECOMMENDED SCREENING AND MANAGEMENT

 

This year, differing from that of last year, NCCN Guidelines included the same screening protocol for all Lynch syndrome patients, regardless of mutation. The NCCN protocol is a minimum standard.  As noted, physicians may add other screenings as they feel necessary.  The guidelines are basic, due to limited research into the cancers and care of those with Lynch syndrome.

 

COLONOSCOPY: 

Annually, beginning at age 20-25, or two to five years younger than the earliest age of diagnosis in the family, whichever comes first.

 (NCCN ) state colonoscopy to be administered  two to five years prior to the earliest age of diagnosis in the family, and to repeat every 1-2 years.

There is data to suggest aspirin may decrease the risk of colon cancer in LS, however at this time the data are not sufficiently robust to make a recommendation for its standard use.

 

NCCN Guidelines reflects:  There are data to suggest that aspirin may decrease the risk of colon cancer in LS, however, at this time, the data are not sufficiently robust to make a recommendation for its standard use. 

 

Endometrial Sampling: Annually, beginning between ages 30-35

NCCN states, "There is no clear evidence to support screening for endometrial cancer for LS.  However annual office endometrial sampling may be an option."  Hysterectomy and bilateral salpingo-oopherectomy is a risk reducing option by women who have completed childbirth.

 

CA-125: For Ovarian Cancer

NCCN Guidelines state, "However while there may be circumstances where clinicians may find screening helpful, data do not support routine ovarian screening for LS. 

 

Transvaginal Ultrasound/Endometrial Biopsy : For Endometrial and Ovarian Cancer: Annually beginning ages 30-35

NCCN Guidelines state, "Transvaginal ultrasound for ovarian and endometrial cancer has not been shown to be sufficiently sensitive or specific as to support a reommendation, but may be consideration at the Clinician's discretion.  Serum Ovarian 125 is an additional screening test with caveats similar to transvaginal ultrasound." 

 

Ultrasonography With Cytology: Annually, beginning at age 25-35

NCCN Guidelines state, "Consider urinalysis starting at 25-30 years old."

 

Gastroscopy: Annually for individuals with family history of Lynch gastric cancers.

NCCN Guidelines state, "There is no clear evidence to support screening for gastric, duodenal, and small bowel cancer for LS.  Selected individuals or families or those of Asian descent may consider EGD with extended duodenoscopy (to distal duodenum or small jejunum.)"

 Examination and Review: Family History Review, Discussion of LS - Annually

NCCN did not address annual family history review or discussion of Lynch syndrome.

 

Dermatological Examination: Including Muir-Torre lesions characterized including, but not all inclusive of sebaceous adenomas, sebaceous epithelioma, basal cell epithelioma with sebaceous differentiation, sebaceous carcinoma and squamous cell cancer (keratoacanthoma type.)

NCCN did not address skin cancers.

 

Prostate Cancer:  NCCN Guidelines did not address any screening measures.

 

Colon Resection: For individuals with active colon cancer that cannot be removed by colonoscopy. Subtotal colectomy favored with preferences of patient actively elicited. Consider more extensive colectomy for patients with a strong family history of colon cancer or young age. (<50) 

 

Full Abdominal Hysterectomy and Bilateral Salpingo Oopherectomy: Discuss as an option after childbearing years to deter the high risk of gynecological cancers. (Recommended by NCCN)

 

Any Other Screening As Deemed Appropriate By the Physician:

Breast cancer has been identified as an integral component of LS based upon mismatch repair germline mutation factors in breast cancer tissues from family members who are not only at high risk, but, moreover, who had Lynch syndrome cancers, such as involving the colorectum. Breast cancer is exceedingly common in the population and, therein, its occurence in Lynch syndrome families could be due to chance, but importantly, a subset will likely be integrally related to a germline mismatch repair Lynch syndrome mutation is some LS families. Therefore, it would be prudent to mount a screening and management program for Lynch syndrome in those families where breast cancer is believed to be an integral lesion.

NCCN Guidelines stated,  "There have been suggestions that there has been an increased risk for breast cancer in LS, however due to limited data, no effective screening techniques have been identified, therefore, no recommendation is possible at this time." 

In respect to pancreatic cancers, NCCN Guidelines state:  "Despite data reading an increased risk for pancreatic cancer, no effective screening techniques have been identified, therefore, no screening." 

Finally, NCCN addressed CNS cancer with:  "Annual physical exam starting at 25-30 yrs; no additional screening recommendations have been made. 

European studies have evidenced prostate cancer as an integral component of LS based upon mismatch repair germline mutation factors. Annual PSA screenings and prostate examinations are a prudent approach for screening of individuals with the Lynch syndrome.

 

Modified 5/18/2014

 


Databases and Laboratories

 

DATABASES AND LABORATORIES:


GeneTests from the University of Washington provides a list of genetics clinics in the United States and internationally. The list can be accessed by clicking on “Clinic Directory” at the top of the GeneTests home page. Clinics can be chosen by state or country, by service, and/or by specialty. State maps can assist in locating a clinic in your area. (Currently Genetests is down, however is expected to return)

 

The National Society of Genetic Counselors offers a searchable directory of genetic counselors in the United States. Search by location, name, area of practice/specialization, and/or ZIP Code.

The National Cancer Institute provides a Cancer Genetics Services Directory, which lists professionals who provide services related to cancer genetics. You can search by type of cancer or syndrome, location, and/or provider name.

The NCBI offers a database which lists labs and information on the specific gene mutations.

 

InSight, an organization of the top gastro cancer researchers in the world, maintains a database on the mutations and lists some of the cancers of the specific mutations.

 

The Memorial University of Newfoundland has a terrific database of specific mutations and articles directly addressing those mutations.

 

 

 

 


 

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Specific Mutated Genes

IT'S JUST THE TIP OF THE ICEBERG

 

Approximately ten percent (10%) of all cancers are hereditary. It is estimated many more are familial. Finally, 35% of all colorectal cancer is hereditary and familial. These patients need to be identified and receive more extensive cancer screenings. FIT testing is not effective for those with familial conditions. We have most likely only touched the tip of the iceberg in respect to hereditary and familial cancers.

The field of genetics is pioneering and modern medical technology changes daily. What we do know, today, is with early detection and a good screening management program, coupled with prophylactic treatment, many affected by genetic defects, resulting in a high predisposition to cancer, can be saved as a number of the cancers are preventable and treatable before becoming life threatening.

 

Li Fraumeini Syndrome - Breast cancer before the age of 50, soft tissue sarcoma, osteosarcoma, brain tumors, lung cancer, adrenal gland cancer, leukemia and other cancers. Genetic defect in the TP-53 gene

Hereditary Breast and Ovarian Cancer Syndrome - HBOC High lifetime risk of breast cancer and of ovarian cancers. Prostate cancer in men.

Cowden Syndrome - Also known as PTEN, Creates a 10% risk to thyroid and a higher than average risk to breast and uterine cancers. It hasn't been extensively studied...

Familial Adenomatous Polyposis (FAP) or Gardner's Syndrome is a colon cancer predisposition syndrome in which hundreds to thousands of precancerous colon polyps (called adenomas) develop throughout the gastrointestinal tract (mostly in the colon and rectum but also in the stomach and small intestine). Attenuated FAP (AFAP) is a milder form of FAP and is associated with increased risk for colon cancer but fewer number of colon polyps. Gardner's Syndrome is associated with the typical number of polyps as in FAP, but also osteomas (benign tumors of the bone) and soft tissue tumors (called desmoids). A second variant, called Turcot Syndrome, is associated with certain brain tumors (different than in HNPCC-Lynch Syndrome). All forms of FAP are associated with mutations in the APC gene.

Von Hippel-Lindau Von Hippel-Lindau Disease (VHL) is a multisystem disorder characterized by abnormal growth of blood vessels (called hemangioblastomas or angiomas). Hemagioblastomas may develop in the retina, certain areas of the brain, the spinal cord and other parts of the nervous system. Other types of tumors can develop in the adrenal gland, kidney and pancreas. Individuals with VHL also have a higher risk to develop certain types of cancer, especially kidney cancer. Nearly all individuals with VHL are found to have mutations in the VHL gene.

Multiple Endocrine Neoplasias Multiple endocrine neoplasia (MEN) syndromes received their name because they predispose people to develop tumors of the endocrine glands. The endocrine system is comprised of glands that secrete hormones into the bloodstream that control numerous processes within the body. The endocrine system is instrumental in regulating mood, growth and development and metabolism, as well as sexual function and reproductive processes.

The major glands of the endocrine system affected by the MEN syndromes are the pituitary, thyroid, parathyroids, adrenals and pancreas. Currently, there are two distinct MEN syndromes: MEN1 and MEN2. In some ways, the two syndromes are similar, but there are important differences.

Reviewed: 5/18/2014

 


 

Diagnostics and Management Publications

"Like with every form of cancer, early detection is what it is all about. ..It can be prevented with testing, and it can be beaten if caught early!"

~ Rod Stewart

 

Diagnosis and management of hereditary colorectal cancer syndromes: Lynch syndrome as a model
Henry T. Lynch, MD, Jane F. Lynch, BSN and Thomas A. Attard, MD



What the Physician Needs to Know About Lynch Syndrome - An UpdateHenry T. Lynch

 

Guidelines for the Clinical Management of Lynch Syndrome by Dr H F A Vasen Department of Gastroenterology, Leiden University Medical Centre and The Netherlands Foundation for the Detection of Hereditary Tumours

 

Lynch Syndrome Wendy Kohlmann, MS and Stephen Gruber, MD, Phd 9/20/2012 Excellent immediate resource guide

 

Endometrial and Ovarian Cancer Screening For Women With the Lynch Syndrome

 

Risk Assessment, Genetic Testing and Management of Lynch Syndrome by Shilpa Grover, MD, MPH and Sapna Syngal, MD, MPH, Boston, Massachusetts

 

Diagnostic Approach and Management of Lynch Syndrome by the American Cancer Society

 

INSIGHT - International Society for Gastrointestinal Hereditary Tumours - International organization that performs research, educates professionals and maintains databases on hereditary gastrointestinal conditions.

 

Hereditary Non-Polyposis Colon Cancer (Excellent Resource) by Dr. Steve Gruber and Wendy Kohlman, MS, Cancer Genetics Clinic, University of Michigan, Ann Arbor, Michigan

NCCN Guidelines (See Page 8 for Lynch syndrome)

Value of MLH1 and MSH2 In the Appearance of Muir-Torre Syndrome Phenotype in HNPCC Patients Presenting Sebaceous Gland Tumors or Keratoacanthomas; http://www.nature.com/jid/journal/v126/n10/full/5700475a.html Giovanni Ponti, Lorena Losi, Monica Pedroni, Emanuela Lucci-Cordisco, Carmela di Gregorio, Giovanni Pelicani and Stephania Seidenari,

  1. 1Department of Internal Medicine, Division of Dermatology, University of Modena and Reggio Emilia, Modena, Italy
  2. 2Department of Pathology, University of Modena and Reggio Emilia, Modena, Italy
  3. 3Department of Internal Medicine, Division of Internal Medicine, University of Modena and Reggio Emilia, Modena, Italy
  4. 4Department of Clinical Pathophysiology, Section of Medical Genetics, University of Florence, Firenze, Italy
  5. 5Division of Pathology, Carpi General Hospital, Carpi, Modena, Italy

Journal of Investigative Dermatology (2006) 126, 2302–2307. doi:10.1038/sj.jid.5700475; published online 6 July 2006

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Modified 5/18/2014

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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THE VERY FIRST LINE OF DEFENSE IN THE SURVIVAL OF LYNCH SYNDROME IS KNOWING ONE'S FAMILY HISTORY

 

Lynch syndrome is inherited through families in an autosomal dominant manner.  This means an inherited mutation of the mismatch repair gene, coupled with a normal gene will produce children that have an estimated 50-50 chance of contracting Lynch syndrome.

 

The ONLY way to diagnose Lynch syndrome effectively is first through a careful review of the family history.  What the physician is looking for are three individuals, two of which are directly related to the third and who have sustained a Lynch cancer. (Colorectal Cancer, Endometrial Cancer, Gastric Cancer, Ovarian Cancer, Hepatobiliary Cancer, Pancreatic Cancer, Ureter Cancer, Renal Pelvic Cancer, Skin Cancer (Muir Torre), Prostate Cancer, some subsets of Breast Cancer and Brain Cancer.)

 

This basically leads the physician to determine whether or not to prescribe genetic counseling and/or genetic testing which, if positive, allows individuals diagnosed with Lynch syndrome to obtain annual screening tests to detect cancers early, when they are often treatable and not life threatening.

 

Generations of a Lynch Syndrome Family - A Personal Story

 

Knowing family histories and sharing them with physicians not only helps protect us in avoiding certain hereditary illnesses and predispositions to chronic conditions but alerts us to possible complications which could occur during surgeries and conditions which can affect recovery.  An added benefit is it allows us to learn of family traditions and stories of the trials and tribulations of our ancestors which can also greatly assist in achieving a strong recovery and survivorship.

A good first step toward this process is to view the free, public resource available through the Surgeon General's Family Health Initiative addressing documenting your family history.  Their site has software available for use to document and print out the family history for family members and the health care provider.  In addition, it has the capabilities for the family history to be downloaded into the medical file in your physician's office.

After reviewing it carefully, sit down with your parents and ask them their medical backgrounds, questions about their lives.

Where were they born?  What ethnicity were they and their ancestors? How and where did they grow up?  Were they raised in the city or on a farm--in a small town or in a major metropolitan area?  How did they get their water -- from a well, or a municipality?  What did they eat and how was it prepared?  What was their life like?  Did they work in factories or spray crops?  When and where were they born?  Were they ever ill or hospitalized?  Did they contract any cancers?  At what age?  If so, where was the cancer located?  Where were they treated?

These questions are extremely important as environmental factors have every bit as much of an effect on cancers as hereditary factors and can provide clues into what familial or inherited cancer condition one may have.  

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Everything is interrelated when it comes to cancer.  Therefore, list every occupation, every situation, everything those ancestors did and when, where and at what age it occurred.

Ask about their parents, grandparents, brothers and sisters, nieces and nephews and pose the same questions you asked about your parents' past and lifestyles.  Every answer they provide will render little clues as to the information you will need to protect yourself and your family.

In many families, adults and other family members have often kept health matters private and may at first appear uncomfortable about answering these questions.  It is important to ask the right questions and to prompt them and job their memories as to where there was removal of colon polyps, skin melanomas, abdominal surgeries, brain disorders and hysterectomies.  Be certain to document each and every one.

When documenting the family history, don't forget to ask about hysterectomies.  Today, one of three women have had a hysterectomy.  This information can significantly provide clues or information to create a direct relationship as endometrial cancer may be equally as prolific in Lynch syndrome as colorectal cancer.

Its also not unusual for family members to have little or no knowledge of how grandparents, aunts and uncles or cousins died so simply ask them when and where...then go to the local library or newspaper office and research the obituary or pull the death certificate from the state or country department of vital records.  After you obtain the family history, draw your pedigree.

When preparing a family history, its a good practice to not limit one's self strictly to Lynch syndrome, but to document every possible condition parents, siblings, children, grandparents, aunts, uncles, nieces, nephews, cousins and ancestors could have had. This process is often eye opening and can provide a totally new perspective in respect to other potential unknown health conditions.

While performing research upon our ancestors and related family members, it only helps us to learn not only how they died but what our ancestors endured in life. This can prove invaluable toward our own sense of survival. The characters of our ancestors can serve as clues as to how they survived unthinkable conditions.  Those clues may dramatically help us weave our way through the survival process.  In reflecting upon how they lived and managed despite incredible adversity, we can draw from their strength.

Once the family history is provided to the doctor, he/she will assess it and by the use of online tools or by expertise, will determine the level of risk for inherited conditions and whether or not to refer you to a genetic counselor or grant a direct referral for genetic testing.

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The taking of a family medical history is considered a "standard of care," taught to all physicians at all medical schools and is considered "good medicine." However in today's quickly evolving technical world, there are an overwhelming number of things for physicians to know.  Therefore, it is reasonable to assume your physician, gynecologist, urologist, dermatologist, obstetrician or pediatrician may not be aware of Lynch syndrome. We may have to provide our care providers with guidelines and resources so they may become familiar with it.

A family medical history will assist health providers in not only determining risk and patterns that may be relevant to one's own health but also provide them with information to recommend prevention tools to reduce the risk of disease, decide what diagnostic tests to prescribe, assess whether or not genetic tests are necessary, diagnose a condition that may not otherwise have been considered, determine whether or not other members of your family are at risk for disease and other measures that could be life saving.

The family medical history won't predict your future health but will allow you to know if you are at high risk for disease, life threatening  or chronic conditions.  The past provides clues to our futures so we and our families may remain happy, healthy and intact.

Researching your family medical history is not only good sense and a loving thing to do, not only as parents, but as a responsibility of a patient to provide to the care provider.

 

LINKS FOR FAMILY HISTORY RESEARCH

Family Medical History Information from Ohio State University

American Medical Association Article on the taking of a Family History

Family History Tools from the National Genome Research Institute

Family History tool by SFGenomics

 

Reviewed 7/20/2012

 

 

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 HELP WANTED

 

Big hearted, strong willed,courageous individuals to help LSI achieve our mission or protecting families and saving lives!  Minimum qualifications:

Must have passion, warmth, commitment, loyalty and dedication for active, busy, exciting position. Work from your own home. Set your own hours. Up and coming organization with great coworkers. Occasional travel ! Meet new people. Terrific Benefits...no pay.

What, no pay?  Yep, no pay...EVERYONE involved with Lynch Syndrome International is a volunteer, from our Executive Board, to our Scientific Medical Board, to our Executive Director, to our Project Managers, to our Regional Representatives.  We are a true, not for profit, 501(c)(3) TOTALLY volunteer organization and propel forward on people power, fueled by passion and commitment to protect families and save lives.

We are seeking volunteers who are willing to fill the following volunteer positions and/or assist with one, two or even all of the following tasks:

Regional Grassroots Coordinators

  • Manage LSI Operations in your region:
  • Facilitate the LSI Buddy to Buddy Program
  • Facilitate Regional LSI Support Groups
  • Arrange and Organize Relay for Life Events
  • Conduct Regional Public Awareness Campaigns for LSI
  • Occasional travel to regional conferences
  • Organize Regional Fundraising Events
  • Report Events and Activities for Newsletter

Internet Communications Coordinator who, by email, will contact public agencies, organizations, medical centers, etc., to link to our website  and maintain content on their sites about Lynch syndrome.

Thousands of Volunteers who will

  • Act as buddies to newly diagnosed previvors and survivors
  • Work with LSI at four annual public awareness events
  • Open up your hearts and your souls to journalists for public awareness events
  • Participate in educational outreach events such as Relay for Life and local conventions.
  • Distribute LSI publications to medical offices and other targeted locations.
  • Participate in Relay for Life Events, promoting Lynch syndrome and hereditary cancers
  • Work at local events, educating others about Lynch syndrome
  • Participate in fundraising efforts for LSI
  • Utilize life and learned skills to enhance the organization, including assisting in writing grants, soliciting organizations for fundraising, making radio spots, filming television ads, writing articles for newspapers, conducting studies of insurance company coverage, medical physicians volunteering services for genetic testing and for screening, researching and providing local resources for individuals with cancers, etc.  There is no end to what one can do to volunteer.
  • Lobby local lawmakers for badly needed changes
  • Engage in organized letter writing campaigns to change guidelines and enhance screening measures.
  • Raise funding for research
  • Get involved in clinical trials, providing needed information to protect families and save future generations.

We realize, as Survivors, sometimes the energy simply isn't as robust as our hearts and our passions.  We understand, admire and respect the priorities of family, friends and simply living life to the fullest, as it should be...so please don't volunteer more than what you can comfortably offer, without jeopardizing any other commitment in your life.  There are many, many survivors who are working as hard as forty hours a week and many who can only do several hours a month.  That is fine...we can all contribute in our own way...WE are the ones who will make the needed changes!

Between all of us, we should be able to move mountains...and win battles...on our terms...one life and one family at a time...

Please This email address is being protected from spambots. You need JavaScript enabled to view it. in order to volunteer!           
 

 

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