Article Index
For Professionals
Characteristics of Lynch Syndrome
Diagnosis and Management
Diagnostic Guidelines
Diagnostic Tools for Professionals
Recommended Screening Guidelines
Genetic Counselors and Laboratories
Specific Mutated Genes
Other Genetic Cancers
All Pages


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



     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, whereupon 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 toward diagnosis of the
Lynch syndrome.




    Lynch syndrome is part of a syndrome known as hereditary nonpolyposis colorectal cancer (HNPCC).  This syndrome includes individuals individuals having Familial Colorectal Cancer Type X, who display no evidence of DNA mismatch repair gene deficiency as well as those who have Lynch syndrome, which is indicated by a defect in mismatch repair genes.

     Approximately 10% of all cancers are hereditary.  Thirty five percent (35%) of colorectal cancers have been stated to be the result of a familial or hereditary condition.  

     The American Cancer Society reports about 145,000 people per year contract colorectal cancer and studies conducted by the James Cancer Center at Ohio State University indicate one in every 35 of those persons are affected with  Lynch syndrome.  

     Geneticists predict approximately 800,000 individuals within the United States, alone, are affected by Lynch syndrome, however it is believed less than 5% of that number have been diagnosed.  It is thought one in every 440 to 550 persons is affected by Lynch syndrome.  

      Relying upon these numbers, it can be reasonably assumed each physician whose practice provides care for 3,000 to 4,000 persons, has five to ten patients affected by Lynch syndrome, and each patient has an average of three to five direct family members and most likely over a dozen second degree family members affected.

      The only way to diagnose these patients is either by taking a family history, to assess risk and arrange for the genetic testing of those patients, or when those patients present with colorectal and endometrial tumors, arrange for pathological testing of those tumors for the characteristics of Lynch syndrome.


The only true form of diagnosis of Lynch syndrome is through genetic testing. During the process, DNA is sequenced seeking out defects in four primary mismatch repair genes, MLH1, MSH2, MSH6, PMS2 as well as within another gene, TACSTD1 ( Epcam) which eits to the right or to the front of the MSH2 gene.  Deletions in the EPCAM gene have been found to silence or turn off the MSH2 gene and in doing so, predisposes the individual to cancers of the Lynch syndrome.




  •    MLH1-MSH2 1,2MSH62 PMS2 3
    CancerGen Pop1 RiskAvg Age RiskAvg Age RiskAvg Age
    --------------------------- ---------------- ------------------- ---------------------
    Colon5.50% 40%-40%44-81 yrs 10%-22%54 yrs 15%-20%51-66 yrs
    Endometrium2.70% 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
    Ovaries1.60% 4%-24%42.5 yrs 1%-11%46 yrs 6%*42 yrs
    Hepatobiliary Tract<1% 1.4%-4%50-57 yrs UnkUnk 6%*Unknown
    Urinary Tract<1% 1%-4%54-60 yrs 


    65 yrs 6%*Unknown
    Small Bowel<1% 3%-8%47-49 yrs Unk54 yrs 6%*59 yrs
    Brain/CNS<1% 1%-3%50 yrs UnkUnk 6%*45 yrs
    Sebaceous Neoplasms<1% 1%-9%Unk UnkUnk UnknownUnknown
    Pancreas<1% 1%-6%Unk 1%-6%Unk UnknownUnknown



1. Kohlman, W Gruber, SB2012 
1,2 Bonatel et al Jama 2011    
3 Sentel, et alGastroentrology 2008  
4 Kastrinos et al Jama 2009    

* Starred Cancers combined = 6% Risk.


     More detailed information on the diagnosis and management of Lynch syndrome is below.  


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


Is Breast Cancer A Part of the Lynch Syndrome?

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 in 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.


What Is The Cost Effectiveness Of Genetic Testing?


*The Cost-Effectiveness of Genetic Testing Strategies for Lynch Syndrome Among Newly Diagnosed Patients with Colorectal Cancer, published online on January 15, 2010 in Genetics in Medicine. Authors: Mvundura M, Grosse SD, Hampel H, Palomaki GE.

Widespread Genetic Testing Appears Cost Effective published online on 1/4/2011 in Cancer Prev Res (Phila) Authors: Dinh, TA, Rosner, BL, Atwood, JC, Boland, CR, Syngal S, Vasan, HF, Gruber, SB, Burt, RW

LSI recommends a two pronged approach toward identifying those with the Lynch syndrome to include 

NCCN Guidelines of January, 2014 recommend all patients who meet a five percent or greter risk threshold for Lynch syndrome are appropriate for testing. (PREMM Model), a recommendation against sequential testing for the five Lynch syndrome genes in lieu of panel testing, and individuals with cancer can proceed directly to sequenced teseting without a complicated tissue screening algorithm.


Modified 3/7/2014


Latest Updates

Newest Articles