Adenoma- A benign polyp that may be pre cancerous.
AmsterdamCriteria: Guidelines to determine who should be referred for Lynch syndrome genetic testing.
Anus- Outlet of the rectum.
At risk- A person at risk has the possibility of having Lynch syndrome due to family history, however has not been tested.
Autosomal dominant- A pattern of inheritance in which an affected individual has one copy of a mutant gene and one normal gene on a pair of chromosomes. Individuals with autosomal dominant diseases have a 50-50 chance of passing the mutant gene and therefore the disorder onto each of their children.
Barium enema- Chalky liquid, resistant to x-rays, inserted into the large intestine which allows the operator to view the interior of the bowel and detect anything unusual.
Base Pair - two nucleotides on opposite complementary DNA or RNA strands which are connected via hydrogen bonds (the center matter connecting each strand of a double helix together into one strand.)
Benign- Not cancerous
Bethesda Criteria: Guidelines to determine who should submit to Lynch syndrome genetic testing and MSI testing.
Biopsy- Removal of tissue for examination under a microscope.
CA-125 - A blood test that assesses the concentration of CA-125, an antigen found in ovarian cancer.
CAT scan- (Computerized Axial Tomography) - a form of x-ray that shows the size and shape of body organs layer by layer.
Cecum- The first section of the large intestine (colon).
Chemotherapy Neuropathy - nerve damage primarily in the hands, feet, arms and legs, resulting from chemotherapy.
Chromosome- Contains the genetic material of a cell (genes). The normal number of chromosomes in a human cell is 46 (23 pairs).
CIPN:Chemotherapy Induced Peripheral Neuropathy (See Chemotherapy Neuropathy)
Codon: Three adjacent bases on a DNA molecule determines the position of a specific amino acid protein molecule during protein synthesis.
Colectomy- The surgical removal of the colon (large intestine).
Colon - (Large intestine, large bowel), About five to six feet long, it comprises the last section of the colon and includes the cecum, ascending colon, transverse colon, descending colon and sigmoid colon.
Colonoscopy- Also known as "scope," it is an examination of the inside of the entire colon by use of a flexible tube, about five feet in length. The tube has a light source, a magnifying eye glass and an open channel through which air can be passed and biopsies can be taken.
DNA- (Deoxyribonucleic Acid). The molecule that contains the code for the genetic blueprint. It is found in the nucleus of cells.
Duodenum - The first part of the small intestine, about twelve to fifteen inches long.
Endometrial Aspirate - Extraction of tissue from the uterine lining, by suction, for examination.
Endometrium- The mucousy membrane composing the inner layer of the uterine wall.
Epcam Deletion: On chromosome 2, the EPCAM gene lies next to the MSH2 gene. Each gene provides instructions for making protein. The EPCAM gene causes the MSH2 gene to be turned off, by a mechanism called promoter hypermethylation. It causes too many methyl groups to be attached in the promoter region and they attach to the MSH2 gene, resulting in less protein produced in epithelial cells. Loss of this protein results in loss of DNA repair.
Esophagogastroduodenoscopy (EGD, Upper Endoscopy)- Examination by use of a flexible tube passed through the interior of the upper GI tract (esophagus, stomach, and duodenum). The tube has a light source, a magnifying eye glass, and an open channel through which a biopsy can be taken.
ET- Enterostomal Therapist; a specialist, often a nurse, who assists individuals who wear an external abdominal appliance to collect body waste.
Familial Cancer - Cancer that occurs in families more often than would be expected by chance. These cancers often occur at an early age, and may indicate the presence of a gene mutation that increases the risk of cancer. They may also be a sign of shared environmental or lifestyle factors.
FAP (Familial adenomatous polyposis)- An inherited disorder of the gastrointestinal tract in which there are 100 or more pre cancerous polyps.
Flexible sigmoidoscopy- A test in which a flexible tube about 2 1/2 feet in length is used to examine the rectum and lower part of the large bowel. The tube has a light source, a magnifying eyepiece, and an open channel through which air can be passed and a biopsy taken.
FOBT Test: Fecal Occult Blood Test is a non-invasive "at home" test, used to detect hidden blood in the stool and often utilized for colon cancer screening.
Gastroenterologist - A physician who specializes in the gastrointestinal tract.
GI (gastrointestinal) tract- Consists of the esophagus, stomach, small intestine (22-25 feet in length), and large intestine (5-6 feet in length).
Gene- A basic unit of heredity with each occupying a certain, specific place on a chromosome.
Genetic Testing - A blood test assessed by a lab to determine if certain Lynch syndrome mutations exist.
Geneticist- A physician who specializes in genetics.
Germline Mutation- Same as hereditary mutation, called germline because hereditary mutations come egg and sperm cells, which are also called germ cells.
Glioblastoma- A type of primary malignant brain tumor sometimes associated with Lynch syndrome.
Gynecolgist- A physician that specializes in women's cancers.
Hemoccult test- A test using specially treated cardboard slides to check for hidden blood in the stool.
Hereditary- Genetically transmitted from parent to children.
hMLH1, hMSH2, hPMS1, hPMS2- The abbreviated names of some of the more known genes that, when abnormal, cause HNPCC. They are located on chromosomes 2, 3, and 7.
HNPCC(Hereditary Nonpolyposis Colorectal Cancer) - The name of a genetic condition which encompasses Lynch syndrome AND Familial Colorectal Cancer Type X, a familial hereditary cancer condition.
Hysterectomy- Surgical removal of the uterus.
IHC Testing - (See Immunohistochemistry)
Ileoanal pull-through (pelvic pouch procedure, ileoanal anastomosis procedure)- Removal of the colon and the lining of the rectum, leaving the underlying anal muscles, or sphincters. The last part of the small intestine is joined to the anus and an internal pelvic pouch is created.
Ileorectal anastomosis- Removal of the colon and joining of the last part of the small intestine (ileum) to the rectum.
Ileostomy (proctocolectomy)- Removal of the colon, rectum, and anus. An opening is then made from the ileum through the abdominal wall.
Ileum- The last part of the small intestine, 12-15 feet long.
Immunohistochemistry- Also known as IHC. Pathology test of tumor involving staining tumor tissue samples to determine the presence or the absence of certain proteins which may reveal which mutated genes caused the cancer.
Inflammation - Chronic inflammation can trigger the immune system to battle against a persistent infection or bacterium and can contribute to the development of cancer.
Jejunum- The middle part of the small intestine, 8-10 feet long.
Karyotype- A picture of the chromosomes.
Keratoacanthoma- False skin cancer, appearing like a little volcano
LSI- Abbreviation for Lynch Syndrome International
Lynch Syndrome I & II- Another name for the inherited condition, HNPCC.
Malignant - Cancerous
Marker- A physical abnormality that may indicate the presence of, or may predict the future occurrence of a specific disorder in an individual.
Metastasis- Spread of cancer by the lymphatics or bloodstream to other sites in the body.
Microsatellite: Strand of DNA consisting of a sequence of repetitions of one to six base pairs in length.
Microsatellite Instability - Condition created by damaged DNA due to defects in the normal DNA repair process.
MisMatch Repair Gene - Genes that contain mismatch repair proteins that check for and repair mistakes made in the production of new DNA. When a mismatch repair gene becomes altered, as in Lynch syndrome, it ceases to make proteins or ceases to work properly, allowing cancers to develop.
Missense Mutation: A missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. This can render the resulting protein nonfunctional.
MMR- Mismatch Repair
MRI- A procedure in which radio waves and a powerful magnet linked to a computer is used to create detailed pictures of areas inside the body. These pictures can show the difference between normal and diseased tissue.
MSI- Pathology test of a tumor to determine if instability or other qualities of Lynch syndrome exist.
Muir Torre - A rare inherited skin disorder associated with mutations in mismatch repair proteins, hMSH-2 and hMLH-1, which predispose affected patients to cancer malignancies.
Mutation- A change in a gene which may result in a specific disorder.
Non-Invasive- A procedure in which nothing enters the body (i.e., saliva DNA testing)
Nonsense Mutation: a genetic mutation in a DNA sequence that results in a shorter, unfinished protein product which occurs when a premature nonsense or stop codon is introduced into the DNA sequence. When it is translated into protein, the protein is incomplete short of the normal therefore, most of these mutations resulted in nonfunctional proteins.
Oncologist – A physician who specializes in treating cancers
Ostomate- A person with an ileostomy (or colostomy).
Palliative Care - Medical or comfort care that reduces the severity of a disease or slows its progress rather than providing a cure, i.e., if surgery cannot be performed to remove a tumor, radiation treatment might be tried to reduce its rate of growth, and pain management could help the patient manage physical symptoms.
Pathologist: A physician who examines tissues and fluids to diagnose disease to assist in making treatment decisions
Pedigree- family tree; genealogy.
Polyp- nonmalignant growth of tissue protruding from the mucous lining of an organ such as the nose, bladder, or intestine. Also called polypus
Polyposis- See FAP above.
Port - implanted device, below the skin, allowing a catheter to be attached to infuse medicines and fluids such as chemotherapy into the body and to allow blood to be drawn out.
Previvor- An individual diagnosed with Lynch syndrome but whom has not contracted a cancer.
Primary Brain Tumor - tumor that originates in the brain or spinal cord tissue rather than spreading to the brain from another part of the body.
Proband: First individual identified in a family that has a specific hereditary disorder.
Prophylactic: A preventative measure
Propositus/Proposita- (Proband; Index case). The first individual to be identified in a family that has a specific hereditary disorder.
Sarcoma - tumor of the soft tissue or bone
Sebaceous Adenomas- Non cancerous skin tumor of an oil producing gland
Sebaceous Carcinoma - Cancerous skin tumor of an oil producing gland
Sebaceous Epithelioma - A benign tumor of the epitheliom of the sebaceous gland containing basal or germinal cells.
Salpingo-oophorectomy- Removal of the ovary and its Fallopian tube.
Sporadic Cancer: Cancer occurring in people with no family history and no inherited cause.
Staging- Levels of cancer advancement in the body.
Stoma- Artificially created opening in the abdomen.
Surveillance - Regularly scheduled tests to detect cancer
Survivor- Individual diagnosed with Lynch cancer and has contracted a Lynchcancer.
Syndrome- A collection of abnormal physical characteristics occurring in an individual
Transvaginal Ultrasound - High-resolution images of the uterus and ovaries; may be used to screen for endometrial or ovarian cancer
Urine Cytology - Examination of the urine to detect cancer and inflammatory disease in the urinary tract.
Urologist- A physician who specializes in the urinary tract.
VUS - A variant of uncertain significance (VUS) is a genetic sequence change which association with hereditary risk is currently unknown. Persons with a VUS should be managed as though they have Lynch syndrome.
Saturday, 16 February 2013 | 2393 hits
WELCOME TO THE LSI LIBRARY!
Offering a host of resources on Lynch syndrome.
Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts. Gut. 2013 Jun;62(6):812-23. doi: 10.1136/gutjnl-2012-304356. Epub 2013 Feb 13.
EGAPP Recommendations Translation Updated July, 2012
Revised Bethesda Criteria, 2004
Amsterdam II Criteria
American College of Gastroenterology Guidelines February 2009
AGA Guidelines for Colorectal Cancer March 2008
Guidelines Tor The Clinical Management Of Lynch Syndrome by Dr. Hans Vasen 2007
Society of Gynecological Oncologists 2007 (More detailed information)
Practice Parameters of Patients with Dominantly Inherited Colon Cancer the American Society of Colon and Rectal Surgeons 2003 Update 2006
Genetic Counseling Considerations In the Evaluation of Families for Lynch Syndrome-A Review - Journal of Genetic Counseling, National Society of Genetic Counselors, Inc. 2010
NCCN Guidelines - Need to Register To Obtain Access
NCHPEG Tools and Guide PDFs 2013
CLINICAL TRIALS AND REGISTRIES
One of the greatest ways we could pay forward for everything those who have cared for us have done in order to enhance our quality of life is to enroll in Familial Cancer Registries and Clinical Trials so future generations may continue to protect their families and save lives.
Please become involved in these activities as they are the most important lifesaving measures taken today.
Familial Cancer Registries
Italy: Registro Tumori Collorettali
Lynch Syndrome CAPP3 Aspirin Study, Preparing to Recruit 3,000 Individuals To Determine Daily Dose of Aspirin to Reduce Lynch Syndrome Tumors In Those With Lynch Syndrome. Register Now for Study Information Once Study Is Released. Physician Information and Recruitment.
Lynch Syndrome Clinical Trials
National Institute of Health Clinical Trials - Includes Not Yet Recruiting, Recruiting, In Process and Completed Trials for Lynch Syndrome.
Study by Ohio State University for Cryopreservation of Eggs For Women Undergoing Treatments or SurgeriesWhich May Affect Fertility
Study by Helen and Harry Gray Cancer Center at Hartford Hospital (Connecticut) regarding Hyperbaric Oxygen and Ability to Improve Erectile Function Following Surgery for Prostate Cancer
Massachusetts General Hospital - Preoperative Staging of Pancreatic Cancer Using Super Paramagnetic Iron Oxide Magnetic Reasonance Imaging
Pfizer, Institut National du Cancer (France)- Biological, Pathological and Imagery Markers In The First Line Treatment Of Metastatic Clear Cell Renal Cell Carcinoma
Axo-Gen, Vanderbilt Ingram Cancer Center, Nashville, TN Nerve Reconstruction In Individuals Using Avance In Subjects Who Undergo Robotic Assisted Prostatectomy For Treatment of Prostate Cancer
Eisai, MD Anderson, Houston, TX - Dalteparin for Venous Thromboembolism (VTE) Prophylaxis in Pancreatic Cancer Patients
European Association for Endoscopic Surgery (Italy) - Transanal Endoscopic Microsurgery vs. Endoscopic Submucosal Dissection For Large Rectal Adenomas
Hospital Donostaia, San Sebastian, Spain Study to Evaluate the Efficacy of Pravastatin on Survival and Recurrence of Advanced Gastroesophageal Cancer
Gifu, Japan - Republic of Korea Comparing Covered Self-expandable Metallic Stent (SEMS) Above/Across the Sphincter of Oddi
Seoul National University Hospital - Cyclooxygenase-2 Inhibitor for Adjuvant Anticancer Effect in Patients With Biliary-pancreas Cancer
Universitaetsspital-Basel - Influence of N-Acetylcysteine on Morbidity, Oxygenation and Cytokine Levels in Partial or Total Esophagectomy for Cancer
Santa Clara Valley Medical Center, San Jose, CA. Bowel Preparation for Inpatient Colonoscopy
Novartis - Germany An Open Label, Single Arm Trial to Characterize Patients With Metastatic Renal Cell Carcinoma Treated With Everolimus After Failure of the First VEGF-targeted Therapy (MARC-2
Medical Center of Fudan University - Shanghai New Adjuvant Chemotherapy of Non Resectable Liver Metastasis of Colorectal Cancer Without Bleeding, Obstruction
David C. Pratt Cancer Center at St. Johns Mercy, St. Louis, Missouri Stereotactic Body Radiotherapy for Unresectable Pancreatic Cancer - Stereotactic Body Radiotherapy for Liver Tumors, Stereotactic Body Radiotherapy for Prostate Cancer
Bayer Corporation Study to Observe Safety and Efficacy of Nexavar in Treatment of Kidney Cancer
Buenos Aires, Argentina Epoetin Alfa (Hemax®) Phase IV Study in Chemotherapy Induced Anemia
West China Hospital at Sichuan University Effective Study of Preoperative Short-course Radiotherapy for the Advanced Resectable Rectal Cancer
Daniel Stephen Engeler Safety Study of Bipolar Versus Monopolar Transurethral Resection of Bladder Tumors
Case Comprehensive Cancer Center and the Medicis Pharmaceutical Company: Forehead Scars Following Mohs Micrographic Surgery and Reconstruction for Skin Cancer
Myriad Genetics-Various U.S. Locations Study Comparing Optimized 5-FU Dosing and Standard Dosing in Metastatic Colorectal Cancer Patients Treated With mFOLFOX6
Odense University Hospital - Denmark CUP Project PET/CT Applied Early In the Work Up For Metastasizing Of An Unknown Primary Tumor
Mayo Clinic, Jacksonville, Florida Improving Complete Endoscopic Mucosal Resection (EMR) of Colorectal Neoplasia
NCI - Warrent Grant Magnuson Clinical Center Genetic, Clinical, and Epidemiological Study of Individuals and Families at High Risk of Cancer Focuses on Familial Brain Cancers and Bladder Cancers, Bone Cancers
Bristol-Myers Squibb First-Line Gemcitabine, Cisplatin + Ipilimumab for Metastatic Urothelial Carcinoma
Novartis - Memorial Sloan Kettering BKM120 in Metastatic Transitional Cell Carcinoma of the Urothelium
Glaxo-Smith-Klein Memorial Sloan Kettering Gemcitabine and Pazopanib in Chemotherapy Naïve Patients With Advanced/Metastatic Urothelial Carcinoma Ineligible for Cisplatin-based Chemotherapy
Memorial Sloan Kettering Gemcitabine and Cisplatin as Neoadjuvant Chemotherapy in Patients With High-Grade Upper Tract Urothelial Carcinoma
ImClone Study of Ramucirumab or IMC-18F1 With Docetaxel or Docetaxel Alone as Second-Line Therapy in Participants With Bladder,Urethra, Ureter, or Renal Pelvis Carcinoma
Sanofi- Aventus European Organization of Research and Treatment for Cancer. Efficacy of FOLFOX Verus FOLFOX plus Afibercept in K-ras Mutant Patients with Resectable Liver Metastases (BOS3)
LECTURE AND POWER POINT PRESENTATIONS
Power Point Presentation by Dr. Hans Vasen and Dr. Patrick Lynch, Presented At the Insight Conference
Power Point Presentation by Dr. Henry T. Lynch, MD and Jane T. Lynch, BSN The Extraintestinal Cancers of Lynch Syndrome
Power Point Presentation on MSI - IHC Pathological Tumor Testing
Epidemiology of Colon Cancer, Presented to the San Diego Academy of Family Physicians 11/14/2009
UC San Francisco 2009 Slides MSI Basics for Pathologists - Grener
The Power of Sustainable Changes in Diet and Lifestyle by Dean Ornish, M.D., founder and president of the nonprofit Preventive Medicine Research Institute in Sausalito, California. (A one hour plus program courtesy of MD Anderson Cancer Center.)
Lynch Syndrome: Diagnosis and Screening in 2008 Heather Hampel, MS, GCG; Wendy Frankel, MD; Jonathan Terdiman, MD; Roger C. Haggitt Gastrointestinal Pathology Society Session - May 18, 2008
ASCO Article Outlining Study of Taking Effective Family Histories
CME ACCREDITED CLASSES
Free CME Credits and Classes Through NCHPEG and the AMA - Colorectal Cancer, Is Your Patient At High Risk?
Genetics Cancer Review - Expires 2014 ASCO 1.5 CME Credits $25 - $32
Preimplantation Genetic Testing - Expires 2014 (Cleveland Clinic)
Harvard Medical School: Genetics - Colon Cancer Expires 7/6/2013
CME Genetics: Colon Cancer (Expires 6/17/2012) One hour course, 1 CME, intended to teach indiviudals to identify those with Lynch syndrome as well as discusses screening recommendations. Cost: $20
CME Activity: The Lynch Syndrome Up to date education accredited by the American College of Physicians with faculty involving top experts in Lynch syndrome. Expires 7/19/2013 $260 for one year.
American Medical Association - Identifying and Managing Hereditary Cancer Risk
Genomic Medicine - Family History 1 Credit, Cost $5
Genomic Medicine - Colorectal Cancer
Medscape CME Metastatic Colorectal Cancer Tumor Board (oncologists, surgeons, gastroenterologists, radiologists, interventional radiologists, nurses, pharmacists, and other healthcare professionals who treat and care for patients with advanced/metastatic colorectal cancer.)
Cerebral primitive neuroectodermal tumor in an adult with a heterozygous MSH2 mutation Alexander F. Jeans, Ian Frayling, Bharat Jasani, Lucy Side, Claire Blesing & Olaf Ansorge
Oncologic Issues through Audio Digest Foundation 1 CME Credit
National Center for Biotechnology Information (NCBI) Gene Tests - information on anything and everything that is happening with Lynch syndrome research and technology.
Gene Reviews - Hereditary Non-Polyposis Colon Cancer, an excellent, comprehensive resource compiled by Dr. S. Gruber and Wendy Kohmnan, MS of the Cancer Genetics Clinic, Michigan State University, Ann Arbor, Michigan.
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
National Cancer Institute, 6116 Executive Boulevard, Bethesda, Maryland 800-422-6347 Psychosocial Issues in Hereditary Colon Cancer Syndromes
Risks Of Primary Extracolonic Cancers Following Colorectal Cancer In Lynch Syndrome Sept. 2012
Daily Long Termed Aspirin Use In Lynch Syndrome Carriers Reduces Colorectal Cancers England study conducted by Sir John Burn indicates consistent long termed aspirin use (mean 25 months) at 600 mg a day significantly reduces primary colorectal cancers in those with Lynch syndrome. Substantiates new study to determine effective dosage.
Aspirin Confers Long Term Protective Effect in Lynch Syndrome Patients, Jacqueline K. Beels, Phd.
From the Lancet - Effects of Regular Aspirin On Long Term Cancer Incidence and Metastasis 5/2012
Finnish Researchers ConcludeStudy on LS Mortality
9/5/2012 Multi national study in Spain and in Holland indicates cancer-affected LS patients with the AA genotype have shorter telomeres than those with GG and MMR gene mutation carriers with hTERT rs2075786 are at high risk to develop a LS-related tumor at an early age.
1/2013 Collaborative study on genetic testing on first degree relatives (FDRs): Genetic testing may be underutilized by FDRs at risk for LS. The economic feasibility of screening persons with CRC for LS depends on optimizing family-wide uptake of genetic testing. Future research and clinical efforts should focus on ways to overcome barriers to genetic testing.
DIAGNOSIS AND MANAGEMENT
Guidelines intended to assist physicians and medical professionals in understanding and diagnosing Lynch syndrome developed by the National Society of Genetic Counselors and the Collaborative Group of the Americas-- Addresses germline testing and targeted presumptive testing of tumors 12/2011 (Cost)
Diagnostic Approach and Management of Lynch Syndrome - American Cancer Society
Lynch Syndrome: Barriers to and facilitators of screening and disease management, Hered Cancer Clin Pract. 2011 Sep 7;9:8 addresses a Canadian study which concludes persons with Lynch syndrome experience multiple barriers to disease management and the necessity of a coordinated system of local services capable of providing integrated, efficient health care and follow-up.
The Family History Score Tool Identifies High Risk Families for Colorectal Cancer, from the Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA andThe Sanford R. Weiss, M.D. Center for Hereditary Colorectal Neoplasia, Cleveland Clinic, Cleveland, Ohio 44195, USA 5/25/2010
Calculation of Risk of Colorectal and Endometrial Cancer Among Patients With Lynch Syndrome: Gastroenterology 2009 - Largest study, to date, on the high lifetime risk of cancers of those affected by Lynch Syndrome.
Genetics in Medicine: March/April 2003 - Volume 5 - Issue 2 - pp 84-91 The genetic family history as a risk assessment tool in internal medicine Frezzo, Theresa M. MS; Rubinstein, Wendy S. MD, PhD; Dunham, Daniel MD, MPH; Ormond, Kelly E. MS Methods: Seventy-eight patients seen in a division of internal medicine were randomized into two groups, which completed a questionnaire or underwent a pedigree interview. Chart notes were compared to both study tools. Results: Sixty-two (79.5%) of the 78 participants scored at increased risk for at least one category. Either of the two study tools found significantly more people at high risk (48/78, 61.5%) than the chart review (31/78, 39.7%) (P = 0.01) Conclusions: Approximately 20% of patients in an unselected internal medicine practice were at an increased risk that was not documented in reviewed chart notes. Targeted family history analysis reveals patients who require increased medical surveillance, preventive measures, or genetic counseling/testing.
Genetics Home Reference from Gene Tests from the National Institute of Health.
Lynch Syndrome: Still Not A Familiar Picture, by Hess Fredrick From the World Journal of Surgical Oncology a very nice article articulating the misunderstanding many physicians still have in the diagnosis of Lynch syndrome
The Role of Genetic Assessment in Determining a Patient's Risk (for Physician Assistants) Michael A. Rackover PAC MS and Doug Scott MS - Journal of the American Academy of Physician Assistants
Genetics in Medicine: May 2007 - Volume 9 - Issue 5 - pp 290-297 doi: 10.1097/GIM.0b013e31804b45db The impact of predictive genetic testing for hereditary nonpolyposis colorectal cancer: three years after testing Conclusion: Long-term data indicates appropriate screening and improved psychological measures for non-carriers with no evidence of undue psychological distress in carriers of hereditary nonpolyposis cancer mutations.
From Genetics in Medicine: May 2007 Volume 9 Issue 5 pp 290-297 The impact of predictive genetic testing for hereditary nonpolyposis colorectal cancer: three years after testing Collins, Veronica R. Phd; Meiser, Bettina PhD; Ukoumunne, Obioha C PhD; Gaff, Clara PhD; St John, D. James MD; Halliday, Jane L. PhD Conclusion: Long term data indicates appropriate screening and improved psychological measures for non-carriers, with no evidence of undue psychological distress in carriers of Lynch syndrome.
From Genetics in Medicine, October 2009 Volume 11, Issue 10, pp 728-734 Communication, encouragement, and cancer screening in families with and without mutations for hereditary nonpolyposis colorectal cancer: A pilot study; Ersign, Anne L. PhD; Williams, Janet K. PhD; Hadley, Donald W. MS, CGC; Koehly, Laura M. PhD Conclusion: Respondents who communicated about risk and received encouragement to screen from a great proportion of named family members and those who had a greater proportion of named family members involved in both communication and encouragement were significantly more likely to have a shorter time interval since last colonoscopy. Identifying patterns of interaction within at risk families, regardless of gene mutation satus, may be one avenue for promoting screening adherence.
History and Molecular Genetics of Lynch Syndrome in Family G - A Century Later ---- JAMA Julie A. Douglas PhD, Stephen B. Gruber MD Phd, Karen A. Meister MS CGC, Joseph Bonner MS , Patrice Watson Phd, Anne Krush MS, Henry T. Lynch MD Conclusion: Within the last decade, molecular diagnostic testing has transformed the care of Family G and other Lynch syndrome families in which a pathogenic mutation has been identified.
Prophylactic Surgery to Reduce the Risk of Gynecologic Cancers in the Lynch Syndrome, Kathleen M. Schmeler, MD, Henry T. Lynch, MD, Lee-May Chen, MD, Mark F. Munsell, MS, Pamela T. Soliman, MD, Mary Beth Clark, MSW, Molly S. Daniels, MS, Kristin G. White, BS, Stephen G. Boyd-Rogers, RN, Peggy G. Conrad, MS, Kathleen Yl Yang, MD, Mary M. Rubin, PhD, Charlotte C. Sun, Dr.PH, Brian M. Slomovitz, MD, David M. Gershenson, MD and Karen H. Lu, MD Conclusion: Findings suggest that prophylactic hysterectomywith bilateral salpingo-oophorectomy is an effective strategyfor preventing endometrial and ovarian cancer in women withthe Lynch syndrome.(Since publication, it has been noted by MD Anderson there have been a few cases of endometrial cancer despite hysterectomy, however the conclusion remains the same.)
Risk Assessment, Genetic Testing, and Management of Lynch Syndrome - Shilpa Grover, MD, MPH and Sapna Syngal, MD MPH, Boston, Massachusetts
Prospective Screening for Lynch Syndrome In a Cohort of Colorectal Cancer Surgical Patients in a Community Hospital: Albuquerque and Presbyterian Hospital, Albuquerque, NM Conclusion: A screening protocol for detecting LS in newly diagnosed CRC patients using MMR assessment identified LS in at least 8% of screened patients and in at least of 2.0% of all CRC resected. Clinical suspicion misses a significant proportion of patients who have LS. This protocol is a significant step forward in the timely identification of LS in a community hospital setting.
Diagnosis and Management of Hereditary Colorectal Cancer Syndromes: Lynch Syndrome As A Model, Henry T. Lynch
NationalCenterfor Biotechnology Information (NCBI) Gene Tests providing information on anythingand everything that is happening with Lynch syndrome research and technology.
12/13/2010 Netherlands study indicates individuals with LS are good candidates for chemo prevention. The response of MMR-Deficient tumors to standard chemotherapy and radiotherapy differs from that of MMR-proficient tumors. Efforts should be directed toward designing tailored strategies concerning both chemo prevention and medical cancer treatment for individuals affected with Lynch syndrome.
A excellent study from Kaiser Permanente and the Marshfield Clinic regarding theunderdiagnosis of Lynch Syndrome. May 2012
A study from Canada assessing the barriers to diagnosis and management of Lynch syndrome: Lynch Syndrome Barriers To and Facilitators of Screening and Disease Management 9/2011, Hereditary Cancer in Clinical Practice 2011doi:10.1186/1897-4287-9-8
The Risk of Extracolonic Primary Cancers Following Colorectal Cancer in Lynch Syndrome An international study of 764 carriers of Lynch syndrome. September, 2012
Colorectal And Other Cancer Risks For Carriers and Non-Carriers From Families With A DNA Mismatch Repair Gene Mutation - A Prospective Cohort Study/ An International Study That Is a Must Read Discussing the Risks of Specific Cancers of Lynch Syndrome And One Of The First Comprehensive Studies On The Risk of Breast Cancer Within Lynch Syndrome
MD Anderson studies the spectrum of Lynch syndrome cancers. determining those with LS can present with cancers outside the spectrum of LS. A good paper citing information that may be helpful for diagnosis and screening for patients with Lynch Syndrome. 6/20/2012
UT Southwest article regarding important information on biallelic mutations
Canadian study describes a novel biallelic condition 10/2012
BLADDER CANCER, URETER CANCER, RENAL PELVIS CANCERS
7/25/2012 A study from Canada sends a strong message: . MSH2 carriers should be offered screening for cancer of the entire urothelium, as they are at an increased risk for both bladder AND upper tract cancers
Risk of Urothelial Bladder Cancer In Lynch Syndrome Is Increased, In Particular, Among MSH2 Mutation Carriers JMedGenet2010 Netherlands Study, Radboud University
From Pubmed: Reviews in Urology: 2003 Winter 5(1) 49-53 Urothelial Carcinoma in a Man with Hereditary Nonpolyposis Colon Cancer, by Dean L. Lenz, MD and Lewis E. Harpster, MD, Department of Surgery, Division of Urology, Pensylvania State University, Milton S. Hershey Medical Center, Hershey, Pennsylvania. Synopsis: HNPCC should be considered in any individual with a developed upper tract urothelial cancer or a suggestive family history.
Risk for Urologic Cancer Linked to Risk for Colorectal Cancer WebMD CME Library
Upper Urinary Tract Carcinoma In Lynch Syndrome Cases - Swedish study of U.S. participants from Creighton University data. Majority of participants had MSH-2 and sustained ureter cancer a mean 15.8 years after a primary cancer. Median age was 62. Equal gender ratio and high grade tumors similar to that in the geneal population.
A Study From France: 21.3% Of All Upper Urinary Tract Urothelial Carcinomas May Have Underlying Lynch Syndrome As a Cause. 6/15/2012
Impact of Distal Ureter Management on Oncologic Outcomes Following Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma Collaborated letter on the gold standard for urinary tract urothelial carcinoma. July 2012
8/21/2012 Dr. James Ford of Stanford University addresses the question, "Is Breast Cancer A Part of Lynch Syndrome?" A "Must Read" for genetic counselors and medical professionals
Evidence of Breast Cancer As An Integral Part Of Lynch Syndrome Swiss study of six families of hundreds of persons with 92 female mutation carriers with MLH1 and MSH2 mutations, mean age 49 to 50 years old, consistent with the mean cancer rate of the average population (56.5 years of age) MSI present in 26 of 37 (70.3%) and altered MMR expression in 16 of 22 (72.7%) Lynch syndrome carriers. Conclusion was findings presented a strong molecular evidence for a pivotal role of MMR deficiency in breast cancer development in Lynch syndrome. 10/27/2011
Lynch Syndrome-Associated Breast Cancers: Clinicopathologic Characteristics of a Case Series from the Colon Cancer Family Registry Walsh, Buchanan, Cummings, Pearson, Arnold, Clendenning, WAlters, McKeone, Spurdle, Hopper, Jenkins, Phillips, Suthers, George, Goldblatt, Muir, Tucker, Pelzer, Gattas, Woodall, Parry, Macrae, Haile, Baron, Potter, LeMarchand, Bapat, Thibodeau, Lindor, McGuckin, Young Authors' Affiliation: Familial Cancer Laboratory, Molecular Cancer Epidemiology Laboratory, Queensland Institute of Medical Research, University of Queensland School of Medicine, University of Queensland Centre for Clinical Research, Genetic Health Queensland, Royal Brisbane and Women's Hospital, Herston, Mater Medical Research Institute, South Brisbane, Queensland, Australia; School of Population Health, Centre for MEGA Epidemiology, University of Melbourne, Melbourne, Australia; Department of Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia; South Australian Clinical Genetics Service, North Adelaide, Department of Paediatrics, University of Adelaide, South Australia, Australia; Genetic Services of Western Australia, King Edward Memorial Hospital, Subiaco, School of Paediatrics and Child Health, University of Western Australia, Nedlands, Western Australia, Australia; Clinical Genetics Service, Prince of Wales Hospital, Randwick, New South Wales, Australia; Northern Regional Genetics, Auckland Hospital, University of Auckland, Auckland, New Zealand; Keck School of Medicine, University of Southern California, Los Angeles, California; Dartmouth Medical School, Hanover, New Hampshire; Fred Hutchinson Cancer Research Center, Seattle, Washington; Cancer Research Center of Hawaii, University of Hawaii at Manoa, Honolulu, Hawaii; Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Canada; and Mayo Clinic, Rochester, Minnesota.
Unusual Presentation of Lynch Syndrome London Study 2009, Male Breast Cancer
Lynch Syndrome Associated Breast Cancers - Clinicopathological Characteristics Of A Case Study From The Colon Cancer Registry - David Walsh, MD, Familial Cancer Laboratory Queensland 51% of all breast cancers in individuals with Lynch syndrome indicated MMR deficiency. Breast cancer may therefore represent a valid tissue option for the detection of MMR deficiency in which spectrum tumors are lacking.
Early Onset Breast Cancer In A Lebanese Family With Lynch Syndrome Due to MSH-2 Gene Mutation, Rizk Hospital, Beirut, Lebanon 5/28/2009
Lynch Syndrome- The Influence of Environmental Factors On Extracolonic Cancer Risk on hMLH1 C.c1528T Mutation Carriers and Their Mutation Negative Sisters South Africa Study - Extracolonic cancer occurred in 14 percent of the mutation carrier females. Breast cancer was the most extracolonic cancer.
Colorectal And Other Cancer Risks For Carriers and Non-Carriers From Families With A DNA Mismatch Repair Gene Mutation - A Prospective Cohort Study/ An International Study That Is a Must Read Discussing the Risks of Specific Cancers of Lynch Syndrome And One Of The First Comprehensive Studies On The Risk of Breast Cancer Within Lynch Syndrome
J Clin Oncol 30, 2012 (suppl 4; abstr 413) Breast Cancer In Irish Families With Lynch Syndrome Breast cancer occurred at an early age and was more common than prostate cancer in Irish Lynch Syndrome pedigrees. All reported breast cancer cases were in kindreds with MSH2 or MSH6 mutations. Enhanced breast cancer screening may be warranted in certain Lynch Syndrome kindreds.
Breast Cancer and South African Females, 2010, Lynch syndrome: the influence of environmental factors on extracolonic cancer risk in hMLH1 c.C1528T mutation carriers and their mutation-negative sisters. Breast cancer was double that of those studied without mutations.
COLORECTAL CANCER/SMALL INTESTINE
Small Bowel Adenocarcinoma Phenotyping, a Clinical Prognostic Study, Suggests molecular alterations in small bowel adenocarcinomas (SBA) are closer to those in colorectal cancer (CRC) than gastric cancer, with low levels of HER 2 overexpression and high frequencies of KRAS mutations. Seemingly higher frequency of MMR deficiency (dMMR) than in CRC may be explained by higher frequency of LS in SBA patients. A dMMR phenotype was significantly associated with a non-metastatic tumour (P=0.02). A trend for a good prognosis and a duodenum or jejunum primary site was associated with dMMR.British Journal of Cancer advance online publication, 5 November 2013; doi:10.1038/bjc.2013.677 www.bjcancer.com.
6/2012 University of Groeningen, Netherlands, discusses small bowel surveillance for Lynch syndrome. Recent data indicates capsule endoscopy shows promising results for those with Lynch syndrome and who have a 5% lifetime risk of contracting small bowel cancer.
Parent of Origin Effects On Age At Colorectal Diagnosis Large collaborated study of many institutions concluded affected daughters of affected fathers were, on average, younger than affected sons of affected mothers. Results need confirmation in an independent study before cliinical significance can be determined.
Distinct Mutations in MLH1 And MSH2 Genes in Hereditary Non-Polyposis Colorectal Cancer HNPCC Families From China
1/2011 According to Aukland, New Zealand study, individuals with more extensive colonic resections have a lower risk of metastasized cancers than those receiving less extensive resections.
DNA Repair System Affects Colon Cancer Recurrence and Survival - Mayo Clinic Study data of more than 2,000 clinical trial patients who had Stage 2 and Stage 3 cancers, and were treated with 5FU chemotherapy protocol, concluded patients with mismatched repair had lower rates of tumor recurrence, longer remissions, fewer metasteses and better survival rates compared to those without defects.
12/2010 Expeditious colonoscopy following discovery of mutation status in patients may benefit newly identified mutation carriers by addressing objective risks for cancer and alleviating underlying emotional distress responses to genetic risk information.
Impact of Colonoscopy Screening On Individuals At High Risk for Hereditary Nonpolyposis Colorectal Cancer HNPCC Spain - Conclusion, Colonoscopy is effective in detecting colorectal adenomas and cancer in individuals with HNPCC - Men have a greater number of colorectal adenomas 2011
The Impact Of Colonoscopy Screening In Male And Female Lynch Syndrome Carriers With An MSH-2 Mutation A study from Newfoundland Canada Study of repeat cancers between screening intervals. Within two years of a colonoscopy, 20% of the males and 7% of the females developed an interval of CRC. CRC development may further be reduced by decreasing the interval to one year and improving quality of colonoscopy.
Infiltration Of Lynch Colorectal Cancers By Activated Immune Cells Associates With Early Staging Of The Primary Tumor And Absence Of Lymph Node Metastases Leiden University Medical Center, 1/18/2012 Conclusion: The immune system assumes an important role of counteracting the progression of Lynch colorectal cancers and in selecting abnormal HLA Class I phonetypes. Findings support the development of clinical strategies that explore the hosts natural anti-tumor immune responses.
Colonoscopic screening at 3-year intervals more than halves the risk of CRC, prevents CRC deaths, and decreases overall mortality by about 65% in HNPCC families.Controlled Fifteen Year Trial on Screening For Colorectal Cancers In Families With Hereditary Polyposis Colorectal Cancer. May 1, 2000 Helsinki University Central Hospital, Helsinki
Colonoscopic surveillance reduces the risk of colorectal cancer in people with a strong family history. This study confirms that members of families with hereditary non-polyposis colorectal cancer require surveillance with short intervals. Prevention of Colorectal Cancer By Colonoscopic Surveillance in Individuals With A Family History of Colorectal Cancer: 16 Year Prospective Follow Up Study Family Cancer Group, Cancer Research UK Colorectal Cancer Unit, St Mark's Hospital, Harrow, Middlesex HA1 3UJ. BMJ 11/5/2005
1/2013 Rectal Cancer and the Lynch syndrome: ...less common than colon cancer,RC is an important component of LS and may be overrepresented in MSH2 mutation carriers. Given high risk of synchronous or metachronous cancers, appropriate surveillance for second malignancies is necessary.
ENDOMETRIAL, CERVICAL AND UTERINE CANCERS
Genetic Testing Strategies in Newly Diagnosed Endometrial Cancer Patients Aimed at Reducing Morbidity or Mortality from Lynch Syndrome In the Index Case or Her Relatives (Allison Stewart, PhD, CDC Consultant) 9/16/2013
Risk of Colorectal Cancer after Diagnosis of Endometrial Cancers: A Population-Based Study article by Science Daily October, 2012
7/2012 From Advances in Anatomic Pathology: The risk of gynecologic malignancy in women with LS approaches and even exceeds that of CRC. Gynecologic malignancies are often the sentinel cancers in these patients. Article reviews the morphologic and clinical features/schemas in LS EC and highlight limitations of restrictive aged-based screening strategies, uncertainty in current clinical schemas and equivocal results of morphologic studies of LS EC. With uncertainty of histologic and clinical schemas, and following developments in CRC, reflex testing of all/vast majority of newly diagnosed EC for LS should be considered.
8/2012 From the Archives of Gynecology and Obstetrics, study reinforces endometrial sampling is essential for women with Lynch syndrome.
8/2012 From Obstetrics and Gynecology: Genetic Testing for Lynch Syndrome, An Inherited Cancer of the Bowel, Endometrium and Ovary - Very nice article with good forms for taking family histories and a nice graph of a standard management plan.
Molecular Analysis of endometrial pathogenesis in Lynch syndrome, J Clin Onco 29 2011, MD Anderson, Ottawa University, concluded hyperplasia is part of the pre-invasive spectrum of LS associated EC. While PTEN loss was common in both LS and sporadic EC, PIK3CA and CTNNB1 mutations were more frequent in sporadic EC than LS EC. Our results indicate that loss of PTEN expression is an early event in sporadic EC and that other common mutations in sporadic EC may have a lesser role in LS associated EC development.
Association of Lynch Syndrome and Risk of Invasive Cervical Cancer, 2010 ASCO Conference, J Clin Oncol 28:15S 2010 Conclusion: Cervical cancer is associated with Lynch syndrome and the histology of cervical cancers in MMR mutation carriers may vary from expected population standards.
Primary Peritoneal Cancer After Bilateral Salpingo-Oophorectomy in Two Patients With Lynch Syndrome. Schmeler, Kathleen M, MD, Daniels, Molly S; Soliman, Pamela T, MD MPH; Broaddus, Russel R, MD PhD; Deavers, Michael T. MD; Vu, Thuy M. MS; Chang, George J. MD, MS; Lu, Karen H. MD
Endometrial Cancer and Lynch Syndrome, Moffit Hospital, MD Anderson
Risk Reducing Surgery in Women At Hereditary Risk of Gynaecological Cancer Czech study, 6/2011 Risk reducing Salpingo Oopherectomy or Hysterectomy is the most effective strategy for gynecological cancer prevention in susceptability gene mutation carriers so far.
Risk of Endometrial Cancer For Women Diagnosed With HNPCC Related Colorectal Carcinoma - Conclusion: One quarter of women diagnosed with Lynch Syndrome associated CRC developed EC within ten years. University of Queensland 12/1/2010
Testing Women With Endometrial Cancer To Detect Lynch Syndrome, University of British Columbia 6/2011 Women may not be identified by Amsterdam 2 criteria. IHC triage at any age, having at least 1 FDR, with a Lynch associated cancer, is a cost effective strategy for detecting Lynch syndrome.
US/Canadian study recommends reflex testing for all endometrial cancers. 7/2012
Researchers Propose Screening For Lynch Syndrome In All Patients With Newly Developed Endometrial Cancer 4/2011
Hysteroscopy In Diagnosing Lynch Syndrome Endometrial Cancer Screening In Patients With Lynch Syndrome J Clin Oncol 29: 2011 (suppl; abstr 5108)
Association of Lynch Syndrome and Invasive Cervical Cancer J Clin Oncol 28:15s, 2010 (suppl; abstr 1501)
7/6/2012 Newfoundland study indicates gynecological screening did not result in earlier gynecologic cancer detection and despite screening two young women died from ovarian cancer suggesting that prophylactic hysterectomy with bilateral salpingo-oophorectomy be considered in female mutation carriers who have completed childbearing.
A Swedish and Danish study indicated ovarian cancer with Lynch syndrome presents at young age with early non-serous tumors indicating a family history of colorectal and endometrial cancers should be specifically considered in such cases.
Ovarian Cancer Linked To Lynch Syndrome Typically Presents as Early Onset Non-Serous Epithelial Tumors Gynecol Oncol. 2011 Jun 1;121(3):462-5. Epub 2011 Mar 9.
Endometrial and Ovarian Cancer Screening and Prevention In Women With Lynch Syndrome
11/31/2012 Prevalence of loss of expression of DNA mismatch repair proteins in primary epithelial ovarian tumors Study demonstrated the loss of MMR protein expression in 10.1% of endometriosis-associated ovarian carcinomas.
Risk of Pancreatic Cancer In Lynch Syndrome Families 2009, JAMA Dana Farber, Michigan State, Conclusion: The risk of pancreatic cancer is eight times higher than the risk of the general population
Lynch Syndrome Tied to Breast and Pancreatic Cancer 2/21/2012
Hereditary, Pancreatic and Hepatobiliary Cancers International Journal of Oncology 2011 Paper discussing the risk and studies regarding pancreatic cancer and Lynch syndrome
From the American Journal of Medical Genetics, Part A, Vol 121A Issue 2, Pgs 159-162, pub 3/26/2003, European researchers publish case study of prostate cancer in Lynch syndrome.
Prostate Cancer Found In Lynch Syndrome Patient
Neuendocrine type prostatic adenocarcinoma with microsatellite instability in a patient with Lynch syndrome December of 2010, University of Nebraska Medical Center, Findings suggested HGPIN-NE is a percursor of invasive SCC and also that prostatic SCC can develop in a patient with Lynch syndrome.
Hereditary Prostate Cancer As A Feature of Lynch Syndrome U. Of Mich, Ann Arbor, 3/2011 35 tumors underwent MSI Analysis, 2 of which were MSI high and 1 of which was MSI-low. Conclusion: PCa may arise in Lynch syndrome due to defective DNA mismatch repair.
Hereditary, Pancreatic and Hepatobiliary cancers - International Journal of Oncology, 2011 Paper discussing risk and studies regarding pancreatic cancer and Lynch syndrome.
Manchester UK study discovers a ten fold risk of prostate cancer has been determined with MSH2. Other significant findings are also noted.
Ohio State Study: Prostate cancer incidence was not increased in this relatively large cohort of LS patients.
SKIN CANCER/MUIR TORRE-GLASTIOBLOMA
8/6/2012 Dr. Maxwell Fung, University of California - Davis, discusses IHC - MSI testing of tumors for Muir Torre
2012 Article, University of California-Davis, Mt. Sinai Dermatology Online Muir Torre - Turcot Syndrome overlap?
8/2012 MSH-6 Family Detected With Muir Torre
7/2012 Mismatch Repair Protein Deficiency Is Common In Sebaceous Tumor Neoplasms
7/2012 Polypoid Adenoid Carcinoma Detected in the Efferent Jejunal Loop following gastrectomy in a Muir Torre Patient.
Acute Myloid Leukaemia Associated With Muir Torre Variant Of Hereditary Non Polyposis Colon Cancer (HNPCC) "Implications for inherited and acquired mutations in DNA mismatch repair genes 9/13/2011 British Journal of Haematology , Volume 156, Issue 2, January 2012
Glastiobloma Multiforme In the Muir Torre syndrome: From Johns Hopkins
A New Mutation In Muir Torre Associated With Familiar Transmission Of Different Gastrointestinal Adenocarinomas - Hungary
The Frequency of Muir-Torre Syndrome Among Lynch Syndrome Families: Christopher D. South , Heather Hampel , Ilene Comeras , Judith A. Westman , Wendy L. Frankel , Albert de la Chapelle, JNCI Journal of the National Cancer Institute Advance Access published February 12, 2008
Italian Researchers have discovered prevelance of Muir Torre associated with the liver in a Lynch syndrome family.
From the Journal of the National Cancer Institute, Volume 100, No. 4, pp 277-281, published online 2/12/2008 by the Oxford University Press is of Muir-Torre Syndrome Among Lynch Syndrome Families bythe Division of Gastroenterology, Hepatology and Nutrition (CDS), Department of Pathology (WLF), and theHuman Cancer Genetics Program, Comprehensive Cancer Center (HH, IC, JAW, AdlC), of the Ohio StateUniversity-Columbus, OH; specifically, Christopher D. South, Heather Hampel, Ilene Comeras, Judith A. Westman,Wendy L. Frankel and Albert de la Chapelle.
From the Journal of Investigative Dermatology 7/6/2006, an excellent, comprehensive article on Muir Torre
Screening for Muir-Torre Syndrome Using Mismatch Repair Protein Immunohistochemistry of Sebaceous Neoplasms. IHC testing not recommended unless a personal history or family history of colorectal cancer exists 12/2012
Brain Cancer and the Lynch Syndrome,Genetics Department, University of Helsinki, Finland, September 2012
Anaplastic oligodendroglioma in an adolescent with lynch syndrome, 12/19/2012 Queensland, Australia
THYROID, FIBROUS HISTIOCYTOMA, SARCOMAS, NEUROENDOCRINE TUMORS AND CORTICAL CARCINOMA
7/11/2012 University of Padova, Padua Italy study concludes soft tissue sarcomas could be included In the spectrum of Lynch syndrome, that even if rarely, depend on MMR genes deficiency
Unusual tumors associated with hereditary nonpolyposis colorectal cancer syndrome dated 2004 by MD Anderson concludes individuals with younger onset adrenal cortical carcinoma and anaplastic thyroid carcinoma should be tested for Lynch syndrome.
Malignant Fibrous histiocytoma is a rare Lynch syndrome associated tumor in two German families: German study from Biomedical Research Laboratory, Johann Wolfgang-Goethe University, Frankfurt, Germany, dated 5/20/2011 concludes two patients within two different families with MSH-2 sustained a malignant fibrous histiocytoma.
Sarcomas Associated With HNPCC, according to a study at the Clinical Research Center, Copenhagen, Denmark, dated 1/8/2009 .
Thyroid Cancer In A Patient With A Germline In An MSH-2 Mutation. Case report and Review Of The Lynch Syndrome Expanding Tumour Spectrum Netherlands Observation
Sloan Kettering Study --- Discussion of Unusual Cancers in Lynch Syndrome Including: Peritoneal Mesothelioma; Pancreatic Neuroendocrine Tumor, Pancreatic Acinar Cell Carcinoma, and adrenalcortical carcinoma 7/2012
Fibrous Histiocytoma discovered in two German families with MSH2. (2038 and 932 +- +3A >T) Conclusion...Data further support that patients with Lynch syndrome are at increased risk for rare tumors such as MFH. However, the prognosis compared to sporadic MFH seems to be favorable. 9/2011
A Molecularly Confirmed Neuroendocrine Tumor in Lynch Syndrome, Washington University, St. Louis, MO 7/2012
Inversion of Exons 1-7 of MSH2 Gene Is A Frequent Cause of Unexplained Lynch Syndrome In A Local Population 10/11/2013
MSH2 Mutation Carriers Presents With More Extracolonic Cancers, than MLH1 Mutation Carriers. 10/10/2013
Constitutional Mismatch Repair Deficiency Syndrome-Biallelic Condition: Diversity of the clinical presentation of the MMR gene biallelic mutations 9/26/2013
MSH6 Cancer Risk: Laura Baglietto, Noralane M. Lindor, James G. Dowty, Darren M. White, Anja Wagner, Encarna B. Gomez Garcia, Annette H. J. T. Vriends, Dutch Lynch Syndrome Study Group, Nicola R. Cartwright, Rebecca A. Barnetson, Susan M. Farrington, Albert Tenesa, Heather Hampel, Daniel Buchanan, Sven Arnold, Joanne Young, Michael D. Walsh, Jeremy Jass, Finlay Macrae, Yoland Antill, Ingrid M. Winship, Graham G. Giles, Jack Goldblatt, Susan Parry, Graeme Suthers, Barbara Leggett, Malinda Butz, Melyssa Aronson, Jenny N. Poynter, John A. Baron, Loic Le Marchand, Robert Haile, Steve Gallinger, John L. Hopper, John Potter, Albert de la Chapelle, Hans F. Vasen, Malcolm G. Dunlop, Stephen N. Thibodeau, Mark A. Jenkins Conclusion: For MSH6 mutation carriers, the estimated cumulative risks toages 70 and 80 years, respectively, were as follows: for colorectalcancer, 22% (95% confidence interval [CI] = 14% to 32%) and44% (95% CI = 28% to 62%) for men and 10% (95% CI = 5% to 17%)and 20% (95% CI = 11% to 35%) for women; for endometrial cancer,26% (95% CI = 18% to 36%) and 44% (95% CI = 30% to 58%); andfor any cancer associated with Lynch syndrome, 24% (95% CI =16% to 37%) and 47% (95% CI = 32% to 66%) for men and 40% (95%CI = 32% to 52%) and 65% (95% CI = 53% to 78%) for women. Comparedwith incidence for the general population, MSH6 mutation carriershad an eightfold increased incidence of colorectal cancer (HR= 7.6, 95% CI = 5.4 to 10.8), which was independent of sex andage. Women who were MSH6 mutation carriers had a 26-fold increasedincidence of endometrial cancer (HR = 25.5, 95% CI = 16.8 to38.7) and a sixfold increased incidence of other cancers associatedwith Lynch syndrome (HR = 6.0, 95% CI = 3.4 to 10.7).
8/5/2012 Cancer Risks of the Danish MLH1 Mutation of Lynch syndrome
Fibrous Histiocytoma found in two German Families with MSH2 - 2038C and MSH2 932 +- 3A >_ T. Conclusion....Data further support that patients with Lynch syndrome are at increased risk for rare tumors such as MFH. However, the prognosis compared to sporadic MFH seems to be favorable. 9/2011
China study detects esophaegal cancer risk as a result of polymorphism of MSH-2 and WRN 12/2011
Malignant Fibrous Histicytoma detected in German Families with MSH2, Exon 13 12/2011
Cancer Risks Teased Out In Lynch Syndrome - French study assessed 537 families with MSH1, MSH2 and MSH6 gene mutations to determine risk by age, tumor and other factors. Conclusion: Risks were higher in families with MSH1 and MSH2 had higher risks of cancer and the risk in MSH6 was lower and cancers ordinarily orginated at a younger age
Lynch Syndrome TACSTD1 Family with Predominant Colorectal Cancer: J Clin Oncol 28:15S, 2010 Germline mutations cannot be found in MMRs MLH1 and MSH2 in about 30% of families satisfying the Amsterdam Criteria. Recently, deletions in the TACSTD1 gene have been identified as a cause of LS. Conclusion: Identification of these mutations as a cause of LS allows family members to identify their cancer risk, receive genetic counseling and obtain annual surveillance management. HT Lynch and Others; Conclusion: Identification of TACSTD1 mutations as a cause of LS has important cancer control implications for this and other LS families thereby enabling family members to identify their cancer risk, receive genetic counseling, and enroll in an appropriate cancer surveillance/management program. Extracolonic cancer risk may be decreased in TACSTD1 mutation carriers but this will require further confirmation
Risk of Colorectal and Endometrial Cancers in EPCAM Deletion-Positive Lynch Syndrome: A Cohort Study Netherlands 1/2011 EPCAM Deletion Carriers have a high risk of colorectal cancer and only those with deletions extending close to MSH2 have an increased risk of endometrial cancer.
Epcam Deletion Carriers Constitute A Unique Subgroup of Lynch Syndrome Patients, Netherlands 12/23/2012 Discusses EPCAM deletions, how the size and location of the gene may affect the risk of cancer...
Determining the Frequency of De Novo Germlike Mutations in DNA Mismatch Repair Genes
The Clinical Phenotype of Lynch Syndrome Due to Germline PMS2 Mutations Excellent study explaining in depth the clinical characteristics ofPMS2 mutation carriers, which has not been explored in depth up until this point. by Human Cancer Genetics Program, The Ohio State University Comprehensive Cancer Center Columbus, Ohio Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St John’s, Newfoundland Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington Karolinska Institute, Department of Molecular Medicine, Stockholm, Sweden Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota Department of Medical Genetics, Mayo Clinic College of Medicine, Rochester, Minnesota Queensland Institute of Medical Research, Brisbane, Queensland, AustraliaAdult Clinical Genetics, The University of Melbourne, Victoria, Australia Centre for MEGA Epidemiology, School of Population Health, The University of Melbourne, Victoria, AustraliaJournal of the National Cancer Institute, 2010 102(3):193-201; doi:10.1093/jnci/djp473
Germline Analysis of the hPMS2 Gene in Chinese Families With HNPCC 8/2012
Risks of Lynch Syndrome Cancers for MSH6 Mutation Carriers
From the Journal of the National Cancer Institute, Risks of Lynch Cancers for MSH6 Mutation Carriers Conclusion: We have obtained precise and accurate estimates of both absoluteand relative cancer risks for MSH6 mutation carriers.
Correlation Between Clinical Pathological Parameters and Family History To Detect Mutations in MLH1, MSH2 and MSH6, Spain 2011 Conclusion: The most important clinical feature to predict the presence of a mutation in the genesMLH1, MSH2 and/or MSH6 in families with HNPCC is the diagnosis of endometrial cancer (univariate analysis).
Study indicates Amsterdam criteria and each of the Bethesda criteria were inadequate for identifying MSH6 mutation-carrying kindreds. MSH6 mutations may be more common than currently assumed, and the penetrance/expression of MSH6 mutations, as derived from families meeting current clinical criteria, may be misleading. To increase detection rate of MMR mutation carriers, all cancers in the Lynch syndrome tumour spectrum should be subjected to immunohistochemical analysis and/or analysis for microsatellite instability.
Researchers from Australia find a new method to detect new mutations in mismatch repair genes.
Study from University of Rouen, France, indicates the median age of CRC onset was 43 years, a significant difference of CRC penetrance between males and females and between MSH2 and MLH1 mutation verus MSH6 mutation carriers. Results are in agreement with published studies, which estimate cumulative CRC risk at 70 years is higher in males than females and is lower in MSH6 mutation carriers, compared to those with MSH2 and MLH1.
The Importance of Older Family Members In Providing Social Resources And Promoting Cancer Screenings in Families With a Hereditary Cancer Syndrome: Study by the University of Memphis, 2011. Utilizing the older members of families to facilitate screenings and provide emotional well being of family members may be beneficial. Study indicated younger respondents were more willing to recruit older family members as providers of social resources.
From Sweden, a very good Psycho-Social study Family perspectives in lynch syndrome becoming a family at risk, patterns of communication and influence on relations 9/2012
Impact Of Genetic Testing on Risk-Reducing Behavior in Women AT Risk for Hereditary Gynecologic Cancer Syndromes from Beth Israel Deaconess Medical Center, Boston, Massachusetts and Dana Farber Cancer Institute, Boston, Massachusetts. Conclusion: In the first year after genetic testing, women who tested positive for HBOC or Lynch syndrome increased uptake of prophylactic surgery or screening to reduce their risk of gynecologic cancers. Women with true-negative results do not pursue these unnecessary interventions, whereas those with indeterminate or variant test results do not significantly change their risk-reducing behaviors.
Attitudes Toward Childbearing And Prenatal Testing In Individuals Undergoing Genetic Counseling for Lynch Syndrome: Study of 161 individuals, mean age 46 years, 71 percent women and 53% having sustained cancer, by Dana Farber researchers revealed 80% worried about their childrens risk of cancer but only 9% reported their decision to have children was affected by their family history of cancer.
From Genetics in Medicine: September 2008, Volume 20 - Issue 9 - pp 691-698 Influence of genetic discrimination perceptions and knowledge on cancer genetics referral practice among clinician Lostuter, Katrina J. MS: Sand, Sharon BA; Blazer, Kathleen R. MS; MacDonald Deborarh J. PhD; Banks, Kimberly C. MS; Lee, Carola A. JD; Schwerin, Barbara U. Esq. Juarez, Margaret MD; Uman, Gwen C. PhD, WEitzel, Jeffrey N. MD. Conclusion: Concerns about genetic discriminationand knowledge deficits may be barriers to cancer genetics referrals. Aclinicial education may help promote access to cancer screening and prevention. (Note: 96% viewed genetic testing as beneficial. 75% believed fear of genetic discrimination would cause patients to decline testing. More than 60% were not aware of federal or California laws prohibiting health insurance discrimination. Concern about genetic discrimination was selectged as reason for NONREFERRAL BY 11% of physicians.
National Cancer Institute Page On Psycho-Social Studies Of Those With Lynch Syndrome
ETHNIC AND CULTURE STUDIES
Gynecologic cancer screening and communication with health care providers in women with Lynch Syndrome Clin Genet. 2013 Jul 31. doi: 10.1111/cge.12246
Fam Cancer Lynch Syndrome in High Risk Ashkenazi Jews In Israel 8/30/2013
A novel germline MLH1 mutation causing Lynch Syndrome in patients from the Republic of Macedonia 10/2012
Evaluation of MLH1 1219V Polymorphism in Unrela ted South American Individuals Suspected of Having Lynch Syndrome. 10/2012
6/2012 Study concludes MSI-High appears lower in Korean patients with colorectal cancers
Detection of Hereditary Nonpolyposis Colorectal Cancer (HNPCC) in Non-Caucasian Patients - January 2012, MD Anderson Study of a diverse group of patients over a long period of time, breaking results down to specific cancers.
Characteristics of Lynch Syndrome In Thirteen Hispanic Families: Ricker et.al; Hereditary Cancer in Clinical Practice 2010 8 (Suppl 1) P. 19
Clinicopathologic and Genetic Features of Chinese Hereditary Nonpolyposis Colon Cancer, Shanghai Institute for Biological Science (Abstract)
Prevalence and Characteristics of HNPCC In Immigrant Chinese Cancer Patients (Abstract) Conclusion: MSH-6 has first presentation in patients over age of 50 in Chinese patients. Warrants further study.
8/2012 Germline Analysis of hPMS2 gene in Chinese Families with HNPCC
Esophageal cancer risk is associated with polymorphisms of DNA repair genes MSH2 and WRN in Chinese population 2/2012
Germline MLH1 and MSH2 Mutations In Italian Pancreatic Cancer Patients With Suspected Lynch Syndrome: Conclusion: Only a small subset of Italian pancreatic cancer patients carry pathogenic MMR mutations.
Frequency of Extracolonic Tumors in Brazilian Families With Lynch Syndrome: analysis of an hereditary colorectal cancer institutional registry Breast cancer was the most frequent extracolonic cancer amongst women with endometrial cancer and uterine cervix cancer following. For men, prostate and Gastric Cancers were the most frequent extracolonic cancers.
12/12/2010 A new mutation of Lynch syndrome within Exxon 13 has been found within a Spanish family.
High Risk of Colorectal and Endometrial Cancer in Ashkenazai Families with MSH2 A636P Founder Mutation June 2011 University of Michigan, Ann Arbor, MI Conclusion: Lifetime risk of CRC and EC are high by age 70, 61.62% for men and 61.08% for women with cummulative EC risk of 55.6% for women and an average mean age of diagnosis at 53 years of age.
Women in Tunisia - Tunisian Study MMR repair genes play a significant role in CRC susceptability, more research needed on cause, especially for left hand tumours.
Hereditary Nonpolyposis Colorectal Cancer/Lynch Syndrome In Korean Patients With Endometrial Cancer
7/11/2012 A Unique Mutation in MSH2, Exon 8 Accounts For A Major Portion Of Those With Lynch Syndrome in Sardinia
4/28/2011 Lynch Syndrome In A Predominantly Afrocentric Population, a clinipathological and genetic study... Mount Sinai Hospital, Toronto with University of the West Indies, Mora Jamaica studied 25 patients under 40 with CRC, concluding thirteen percent 13% had mutations with prevalence similar to that reported by the white population.
Screening of the DNA Mismatch Repair Genes of MLH1, MSH2 and MSH6 In A Greek Cohort of Lynch Syndrome Suspected Families BMC Cancer, October 11, 2010
Iranian study of colorectal cancer - Family History of Colorectal Cancer In Iran, Mehr Hospital, Tehran 2005. The family history of cancer is traced in 449 CRC patients of which 112 were 45 yrs or younger and 337 were older than 45 yrs at time of diagnosis. The patients were admitted in two hospitals in Tehran, during a 4-year period.
Results: Clinical diagnosis of HNPCC was established in 21 (4.7%) probands. Family history of CRC was more frequently reported by early-onset than by late-onset patients (29.5% vs. 12.8%, p < 0.001).
Hungarian Researchers discuss the Q48P Mutation of the MLH1 Gene In Three Hungarian Families
Estonian study of colorectal cancer of 180 persons, by use of pathological testing, determines MSI-H and BRAF mutation were observed in 30 and 28 out of all cases, respectively. Several polymorphisms in MLH1 (13); MSH2 (11); MSH6 (10) and PMS2 (15) genes, and a few previously not described variants of unknown significance were found.
8/13/2012 Within a study of 124 unrelated South American individuals, The Val allelic of the I219V polymorphism was found in 51.61% (64/124) of the individuals, with an allelic frequency of 0.3. MLH1 or MHS2 pathogenic mutations were found in 32.81% (21/64) and in 23.33% (14/60) of Val-carriers and non-carriers, respectively. Conclusion: The Val-carrying genotype was frequent in the studied population; however, it does not appear to exert any modifier effect on MLH1 or MSH2 pathogenic mutations and the development of colorectal cancer.
A First Incidence Study of Lynch Syndrome in Italy (6/2012) Of the 430 patients enrolled, 17 (4%) were high risk [4 hereditary non-polyposis colorectal cancer (HNPCC), 12 suspected HNPCC and 1 MUTYH-associated adenomatous polyposis coli (MAP)], 53 moderate risk and 360 mild risk cases. MSI test was performed on 393 tumours, 46 (12%) of them showed MSI-H. In these patients, one MLH1 pathogenetic mutations and two MSH2 pathogenetic mutations were found. Thirty-two (70%) MSI-H cases demonstrated MLH1 methylation and/or BRAF mutation: None showed MLH1/MSH2 mutation. Two biallelic germline MUTYH mutations detected, one with clinical features of MAP. Strong family history of CRC was present in 4% of the enrolled cases; incidence of MLH1/MSH2 or MUTHY mutations was 1.3% and of MSI-H phenotype was 12%. MLH1 methylation and BRAF mutation can exclude 70% of MSI-H cases from gene sequencing.
The Canadian Journal of surgery reports a study conducted of black individuals in Jamaica has indicated thirteen percent of the population had mutations in keeping with Lynch syndrome. 10/2012
The MSH2 c.388_389del mutation shows a founder effect in Portuguese Lynch syndrome families but also occurs de novo in different populations. 11/2/2011
26. Breast cancer in Irish Families Breast cancer occurred at an early age and was more common than prostate cancer in Irish Lynch Syndrome pedigrees. All reported breast cancer cases were in kindreds with MSH2 or MSH6 mutations. Enhanced breast cancer screening may be warranted in certain Lynch Syndrome kindreds.
2005 A study of individuals in Greecereveals The majority of mutations identified in this cohort are found in hMSH2 (77.7%). Furthermore, four of the mutations identified are novel. Finally, a number of novel benign variations were observed in both genes. This is the first report of HNPCC analysis in the Greek population, further underscoring the differences observed in the various geographic populations.
1/2013 Cancer Spectrum in Families from Ireland indicates cancers identified include: CRC, endometrial , gastric, ovarian, renal, breast, prostate, urothelial, NHL, CML, lung, vocal cord, sebaceous carcinoma and cervix. Median age of diagnosis was 44.
1/2013 Ireland study results on LS, of age affected children and affected parents.
MSI - IHC TUMOR TESTING
Identification of Lynch Syndrome Among Patients With Colorectal Cancer 10/17/2012 In an enormous research study involving over 10,000 individuals with Colorectal Cancers, Lynch researchers discovered universal testing of tumors among CRC Probands had a greater sensitivity compared with alternative strategies, including use of the Bethesda criteria.
Current Hypotheses on how Microsatellite Instability Leads to Enhanced Survival of Lynch Syndrome Patients Kristen M. Drescher, Poonam Sharma and Henry T. Lynch, Creighton University
Abstract: High levels of microsatellite instability (MSI-high) are a cardinal feature of colorectal tumors from patients with Lynch Syndrome. Other key characteristics of Lynch Syndrome are that these patients experience fewer metastases and have enhanced survival when compared to patients diagnosed with microsatellite stable (MSS) colorectal cancer. Many of the characteristics associated with Lynch Syndrome including enhanced survival are also observed in patients with sporadic MSI-high colorectal cancer. In this review we will present the current state of knowledge regarding the mechanisms that are utilized by the host to control colorectal cancer in Lynch Syndrome and why these same mechanisms fail in MSS colorectal cancers.
From the Office of Public Health Genomics: The cost-effectiveness of genetic testing strategies for Lynch syndrome among newly diagnosed patients with colorectal cancer. Mvundura M, Grosse SD, Hampel H, Palomaki GE. Genet Med. 2010 Feb;12(2):93-104. Results: Strategies to test for Lynch syndrome in newly diagnosed colorectal tumors using preliminary tests before gene sequencing have incremental cost-effectiveness ratios of $45,000 per life-year saved compared with no testing and $75,000 per life-year saved compared with testing restricted to patients younger than 50 years. The lowest cost testing strategies, using immunohistochemistry as a preliminary test, cost $25,000 per life-year saved relative to no testing and $40,000 per life-year saved relative to testing only patients younger than 50 years. Other testing strategies have incremental cost-effectiveness ratios $700,000 per life-year saved relative to the lowest cost strategies. Increasing the number of relatives tested would improve cost-effectiveness.
Conclusion: Laboratory-based strategies using preliminary tests seem cost-effective from the US health care system perspective. Universal testing detects nearly twice as many cases of Lynch syndrome as targeting younger patients and has an incremental cost-effectiveness ratio comparable with other preventive services. This finding provides support for a recent US recommendation to offer testing for Lynch syndrome to all newly diagnosed patients with colorectal cancer.
The Association of Tumor Microsatellite Instability Phenotype with Family History of Colorectal Cancer Mount Sanai Hospital and Samuel Luenfeld Research, University of Toronto
EGAPP Recommendations April 2011
Preoperative Diagnosis of Lynch Syndrome With DNA Mismatch Repair Immunohistochemistry On A Diagnostic Biopsy - Dec. 2011 33 samples of biopsies taken. Study indicates mismatch repair status is accurate on biopsies allowing preoperative diagnoses of Lynch syndrome before definitive surgery, allowing the patient and the physician more options to determine appropriate protocol.
Psychological Distress In Newly Diagnosed Colorectal Cancer Patients Following Microsatellite Instability Testing for Lynch Syndrome On the Pathologist's Initiative Radboud University Nijmegen Medical Center; Nijmegen, The Netherlands 2/7/2012
Prevalence of Mismatch Repair Deficient Crypt Foci In Lynch Syndrome: A Pathological Study
Routine Universal Screening for Lynch Syndrome in Colorectal Cancer Patients In The Community Setting J Clin Oncol 30, 2012 (suppl; abstr 1512)
Pubmed Links to almost 4,000 studies results and journal articles in respect to Lynch syndrome.
ING Life Insurance speaks of hereditary conditions and Lynch syndrome and insurability
Coding and Billing for Lynch Syndrome
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