Lynch syndrome: Difference between revisions
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== Background == | |||
* Also known as hereditary nonpolyposis colorectal carcinoma (HNPCC) | * Also known as hereditary nonpolyposis colorectal carcinoma (HNPCC) | ||
* Lynch syndrome preferred term since most patients will develop one or several adenomatous polyps | * Lynch syndrome preferred term since most patients will develop one or several adenomatous polyps | ||
* | == Pathogenesis == | ||
* MMR genes: MLH1 | *Caused by inactivation of one of several DNA mismatch repair (MMR) genes | ||
* Mutations in MLH1 and MSH2 account for up to 90% of LS cases | ** MMR genes (4): | ||
***MLH1 | |||
***MSH2 | |||
***MSH6 | |||
***PMS2 | |||
*** Mutations in MLH1 and MSH2 account for up to 90% of LS cases | |||
* Autosomal dominant | * 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.[https://www.cancer.gov/publications/dictionaries/genetics-dictionary/def/autosomal-dominant-inheritance] | ** 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.[https://www.cancer.gov/publications/dictionaries/genetics-dictionary/def/autosomal-dominant-inheritance] | ||
* 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 | == Phenotype == | ||
* This results in total loss of DNA MMR activity in that cell and subsequent microsatellite instability. | *Increased risk of cancer | ||
* Associated malignancies: | ** 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 | ||
* Colon (most common) | *** This results in total loss of DNA MMR activity in that cell and subsequent microsatellite instability. | ||
* Endometrial (second most common) | ** Associated malignancies: | ||
* Urologic (3): Prostate, Urothelial, Adrenal | *** Colon (most common) | ||
* Other: Stomach, Hepatobiliary, Small bowel, Ovarian, Brain (glioblastoma), Sebaceous, carcinomas | *** Endometrial (second most common) | ||
* Inconsistent: Pancreas, Breast | *** Urologic (3): Prostate (inconsistent), Urothelial, Adrenal | ||
*** Other: Stomach, Hepatobiliary, Small bowel, Ovarian, Brain (glioblastoma), Sebaceous, carcinomas | |||
*** Inconsistent: Pancreas, Breast, Prostate | |||
*Identification of LS | |||
**Clinical criteria: Amsterdam II criteria, Revised Bethesda Guidelines | |||
**Models | |||
**Tumour testing: microsatellite instability, immunohistochemistry | |||
== Screening == | |||
* Recommended screening[https://pubmed.ncbi.nlm.nih.gov/25043945/] | |||
** 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 == | == 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. | ||
Revision as of 17:00, 15 December 2021
Background
- Also known as hereditary nonpolyposis colorectal carcinoma (HNPCC)
- Lynch syndrome preferred term since most patients will develop one or several adenomatous polyps
Pathogenesis
- Caused by inactivation of one of several DNA mismatch repair (MMR) genes
- MMR genes (4):
- MLH1
- MSH2
- MSH6
- PMS2
- 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
- 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:
- Colon (most common)
- Endometrial (second most common)
- Urologic (3): Prostate (inconsistent), Urothelial, Adrenal
- Other: Stomach, Hepatobiliary, Small bowel, Ovarian, Brain (glioblastoma), Sebaceous, carcinomas
- 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
- Identification of LS
- Clinical criteria: Amsterdam II criteria, Revised Bethesda Guidelines
- Models
- Tumour testing: microsatellite instability, immunohistochemistry
Screening
- Recommended screening[2]
- 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
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.