Lynch syndrome: Difference between revisions

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== References ==
== References ==
[https://pubmed.ncbi.nlm.nih.gov/25043945/ Giardiello, Francis M., et al.] "Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-society Task Force on colorectal cancer." ''Gastroenterology'' 147.2 (2014): 502-526.
 
* [https://pubmed.ncbi.nlm.nih.gov/25043945/ Giardiello, Francis M., et al.] "Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-society Task Force on colorectal cancer." ''Gastroenterology'' 147.2 (2014): 502-526.
* [https://pubmed.ncbi.nlm.nih.gov/30231390/ Yurgelun, Matthew B., and Heather Hampel. "Recent advances in lynch syndrome: diagnosis, treatment, and cancer prevention." ''American Society of Clinical Oncology Educational Book'' 38 (2018): 101-109.]

Latest revision as of 06:52, 18 April 2024

Background[edit | edit source]

  • Also known as hereditary nonpolyposis colorectal carcinoma (HNPCC)
  • Lynch syndrome preferred term since most patients will develop one or several adenomatous polyps

Pathogenesis[edit | edit source]

  • Caused by inactivation of DNA genes responsible for mismatch repair (MMR)
    • MMR genes (4):
      • MLH1
      • MSH2
      • MSH6
      • PMS2
        • Mutations in MLH1 and MSH2 account for up to 90% of LS cases
          • Alterations affecting the normal function of these genes results in an accumulation of DNA errors and increases the potential for cancer development
  • Autosomal dominant
    • NCI definition: autosomal dominant inheritance is a way a genetic trait or condition can be passed down from parent to child. One copy of a mutated (changed) gene from one parent can cause the genetic condition. A child who has a parent with the mutated gene has a 50% chance of inheriting that mutated gene.[1]

Phenotype[edit | edit source]

  • Increased risk of cancer
    • LS cancers form only after a second hit (by one of several genetic damage mechanisms) occurs within somatic tissue, which causes loss of function to the normal (wild-type) allele inherited from the unaffected parent
      • This results in total loss of DNA MMR activity in that cell and subsequent microsatellite instability.
    • Associated malignancies (11):
      1. Colorectal (20-80%) (most common)
      2. Gynecologic
        1. Endometrial (15-60%) in females (second most common)
        2. Ovarian cancer (1-38%) in females
      3. Urologic
        1. Urothelial (1-18%), includes upper urinary tract and bladder
        2. Prostate
        3. Adrenal§
      4. Other gastrointestinal
        1. Gastric cancers (1-13%)
        2. Hepatobiliary
        3. Small bowel
      5. Skin
        • Sebaceous adenoma, sebaceous epithelioma, sebaceous adenocarcinoma, keratoacanthoma, and squamous cell carcinoma[2]
      6. Brain
      7. Inconsistent: Pancreas, breast, (prostate)

Diagnosis and Evaluation[edit | edit source]

  • Clinical criteria: Amsterdam II criteria, Revised Bethesda Guidelines
  • Models
  • Tumour testing: microsatellite instability, immunohistochemistry

Screening[edit | edit source]

  • Recommended screening[3]
    • Colonoscopy
    • Pelvic exam with endometrial sampling
    • Transvaginal ultrasound (ovarian)
    • Esophagogastroduodenoscopy with biopsy of the gastric antrum
    • Urinalysis
      • Limited data to support urinary screening
    • Routine screening of the prostate and breast cancer is not recommended beyond what is advised for the general population

References[edit | edit source]