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
- Mutations in MLH1 and MSH2 account for up to 90% of LS cases
- MMR genes (4):
- 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):
- Colorectal (20-80%) (most common)
- Gynecologic
- Endometrial (15-60%) in females (second most common)
- Ovarian cancer (1-38%) in females
- Urologic
- Urothelial (1-18%), includes upper urinary tract and bladder
- Prostate
- Adrenal§
- Other gastrointestinal
- Gastric cancers (1-13%)
- Hepatobiliary
- Small bowel
- Skin
- Sebaceous adenoma, sebaceous epithelioma, sebaceous adenocarcinoma, keratoacanthoma, and squamous cell carcinoma[2]
- Brain
- Inconsistent: Pancreas, breast, (prostate)
- 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
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]
- 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.
- 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.