What is Lynch syndrome (Hereditary Nonpolyposis Colorectal Cancer)?

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Last updated: April 26, 2025View editorial policy

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From the Guidelines

Lynch Syndrome is a heritable colorectal cancer syndrome that significantly increases the risk of developing colorectal, endometrial, and other cancers, with a lifetime cumulative incidence of colorectal cancer up to 80% and endometrial cancer up to 60%. According to the American Gastroenterological Association Institute guideline on the diagnosis and management of Lynch syndrome 1, Lynch syndrome is the most common heritable colorectal cancer syndrome, accounting for 2% to 3% of colorectal cancers. The syndrome is often underdiagnosed and has an estimated prevalence in the general population of 1 in 440.

Some key points about Lynch Syndrome include:

  • It is caused by mutations in DNA mismatch repair genes, which normally help fix mistakes in DNA during cell division
  • Besides colorectal cancer, Lynch Syndrome also increases the risk of other cancers, including stomach, small intestine, pancreas, biliary tract, ovary, urinary tract, and brain
  • People with Lynch Syndrome typically need earlier and more frequent cancer screenings
  • The condition follows an autosomal dominant inheritance pattern, meaning a person has a 50% chance of inheriting the mutation if one parent carries it
  • Genetic testing can identify Lynch Syndrome, allowing for appropriate surveillance and preventive measures to reduce cancer risk, as stated in the guidelines on genetic evaluation and management of Lynch syndrome by the US multi-society task force on colorectal cancer 1.

From the Research

Definition of Lynch Syndrome

Lynch syndrome is defined as:

  • An autosomal dominant genetic disorder associated with germline mutations in DNA mismatch repair (MMR) genes 2
  • A hereditary cancer syndrome that increases the risk of developing certain types of cancer, including colorectal, endometrial, and other malignancies 3, 4
  • Caused by mutations in the MLH1, MSH2, MSH6, or PMS2 genes, which are responsible for DNA mismatch repair 5, 6

Key Characteristics

  • Associated with a 50%-70% lifetime risk of colorectal cancer and a 40%-60% risk of endometrial cancer 3
  • Increases the risk of other cancers, including those of the small intestine, stomach, pancreas, biliary tract, ovary, brain, upper urinary tract, and skin 2
  • Can be diagnosed through genetic testing and clinical evaluation 2, 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Mismatch repair genes in Lynch syndrome: a review.

Sao Paulo medical journal = Revista paulista de medicina, 2009

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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