Guidelines on Genetic Evaluation and Management of Lynch Syndrome

A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer

Francis M Giardiello MD; John I Allen; Jennifer E Axilbund; C Richard Boland; Carol A Burke; Randall W Burt; James M Church; Jason A Dominitz; David A Johnson; Tonya Kaltenbach; Theodore R Levin; David A Lieberman; Douglas J Robertson; Sapna Syngal; Douglas K Rex


Am J Gastroenterol. 2014;109(8):1159-1179. 

In This Article

Abstract and Introduction


The Multi-Society Task Force, in collaboration with invited experts, developed guidelines to assist health care providers with the appropriate provision of genetic testing and management of patients at risk for and affected with Lynch syndrome as follows: Figure 1 provides a colorectal cancer risk assessment tool to screen individuals in the office or endoscopy setting; Figure 2 illustrates a strategy for universal screening for Lynch syndrome by tumor testing of patients diagnosed with colorectal cancer; Figures 3,4,5,6 provide algorithms for genetic evaluation of affected and at-risk family members of pedigrees with Lynch syndrome; Table 10 provides guidelines for screening at-risk and affected persons with Lynch syndrome; and Table 12 lists the guidelines for the management of patients with Lynch syndrome. A detailed explanation of Lynch syndrome and the methodology utilized to derive these guidelines, as well as an explanation of, and supporting literature for, these guidelines are provided.


Colorectal cancer (CRC) is a major American health problem that ranks as the second leading cause of cancer death after lung cancer. In the United States, approximately 143,000 new cases are diagnosed each year, and 51,000 Americans die annually from this disorder.[1]

The cause of CRC is multifactorial, with environment and inheritance playing varying roles in different patients.[2] Approximately 70–80% of patients with CRC seem to have sporadic disease with no evidence of an inherited disorder. In the remaining 20–30%, a potentially definable inherited component might be causative.[3]

Lynch syndrome (LS), an autosomal dominant condition, is the most common cause of inherited CRC, accounting for about 3% of newly diagnosed cases of colorectal malignancy.[4–8] The eponym "Lynch syndrome" recognizes Dr Henry T. Lynch, the first author on the original 1966 publication that comprehensively described this condition.[9]

In the early 1990s, mutation of genes in the DNA mismatch repair (MMR) pathway were implicated as the cause of LS,[10–13] and the presence of the mutations now defines the syndrome. Since then, germline testing with increasing sensitivity has been available for patients, as additional genetic discoveries have occurred. When used appropriately, genetic testing for LS can confirm the diagnosis at the molecular level, justify surveillance of at-risk persons, decrease the cost of surveillance by risk stratification, aid in surgical and chemoprevention management, and help in decisions concerning family and career planning. However, when used inappropriately, genetic testing can misinform affected patients with false-negative results and waste patient and societal resources.

The goal of this consensus document is to critically analyze the current literature and provide "best practice" evidence-based recommendations for diagnosis and management strategies to health care providers caring for these patients.