7.5 Genetics of GI Diseases Flashcards
What is the genetic mutation of Gilberts Syndrome?
Variant in the promotor gene that encodes GDP - UGT1A1 leading to 30% of normal levels leading to a rise in bilirubin levels
What is the genetic mutation of Crigler-Najjar syndrome?
complete absence of UGT1A1
What is the genetic mutation of familial adenomatous polyposis?
Inactivation of APC on chromosome 5q21-22 (need inactivation of BOTH alleles - one can be inherited then second hit leading to deletion of other in most cases)
What is the genetic mutation of MUTYH Associated polyposis?
Mutations in the base excision repair gene, mutY homolog (MYH or MUTYH)
What is the genetics of hereditary non-polyposis colon cancer?
germline mutation in DNA mismatch repair (MMR) genes plu activation of a second mutation, loss of heterozygosity or epigenetic silencing
What are the clinical features of FAP?
> 100 polyps
What is the risk of colon cancer and duodenal cancer with FAP
Colon - 100% if untreated
Duodenal - 4-12% lifetime risk
What is the pathology of hereditary non-polyposis colon cancer?
right sided, tumour infiltrating lymphocytes, poorly differentiated, mucinious
How do you identify someone with HNPCC?
3 affected family members in 2 generations with one under 50
what is the main feature of HNPCC?
Microsatellite instability
Who should you consider for HNPCC?
Anyone under 50
other HNPCC cancers
colorectal cancer with MSI-H like histology under 60
colorectal cancer with one or more first degree relatives with HNPCC related tumour with one under 50
What are the 5 pathways involved in colon cancer?
WNT, TGF-beta, PI3K, RTK-RAS, P53
What is the gene involved in chrons?
NOD2 - intracellular receptor for bacterial products
what is the gene involved in UC?
MHC region
