Hereditary Non-polyposis Colorectal Carcinoma Syndrome (HNPCC)
Clinical
- Genetic counseling should be offered before genetic or immunohistologic testing is performed
- Autosomal dominant with variable penetrance
- Increased overall survival for colorectal carcinoma
- Decreased response to 5FU chemotherapy
- Mean age at clinical diagnosis 45 years
- 35% of patients have multiple cancers
- Associated with a lifetime risk of cancer of 70%
- Colorectal adenocarcinoma 70-85%
- Endometrial adenocarcinoma 50-70%
- 3-15%
- Stomach
- Small intestine
- CNS glioblastoma (Turcot syndrome)
- <3%
- Muir-Torre syndrome findings are present in 9% of HNPCC patients
- Sebaceous cutaneous neoplasms
- Keratoacanthomas
- Mutations in MLH1 and MSH2 result in classic HNPCC
- Mutations in PMS2 and MSH6 result in attenuated HNPCC
- Cancers develop 6-8 years later than in classic syndrome
- Homozygous and compound heterozygous mutations lead to cancers in children and young adults (first 3 decades)
- Colorectal and endometrial carcinoma
- CNS, various types
- Leukemias and lymphomas, various types
