HNPCC: Hereditary Nonpolyposis Colon Cancer – Flashcards
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mode of inheritance
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autosomal dominant w/ 80% penetrance
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mutation
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DNA mismatch repair gene mutations
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phenotype
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-colorectal cancer -multiple primary cancers
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incidence
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-50% of people in Western world develop a colorectal tumor by age 70 -10% of these develop colorectal cancer -HNPCC accounts for 3-8% of colorectal cancer
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occurrence of chromosomal instability
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-13-15% of colorectal cancers DON'T have c'some instability -85-90% have insertion or deletion mutations in repetitive sequences called microsatellites
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70% of germline mutation soccur in which 6 genes?
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-DNA mismatch repair genes -MSH2 or MSH6 -MLH1 or MLH3 -PMS1 or PMS2
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which alleles are mutated?
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both must be mutated to cause microsatellite instability
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relationship b/w microsatellite mutations & tumor progression
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-as tumor progresses, more microsatellite loci are mutated -tumor progression is encouraged by inactivation of genes containing microsatellite sequences
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polyp development
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patients w/ HNPCC develop polyps at younger ages than the general population
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where do the tumors arise?
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60-70% of tumors are between the splenic flexure & ileocecal junction
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inherited vs. sporadic colon cancer
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-inherited: less likely to have c'some instability -inherited: behaves less aggressively & is less likely to be aneuploid
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HNPCC associated cancers
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-stomach -small bowel -pancreas -kidney -endometrium -ovaries
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inheritance risk
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patient w/ the gene mutation has 50% risk for children
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Western general population risk
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5-6%, but modified by family history
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influence of family history
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-first degree relative affected: risk = 1.7x -2+ first degree relaves affected: risk = 2.75x -first degree relative affected before age 44: risk = 5x
