Hereditary nonpolyposis colorectal cancer (HNPCC) accounts for approximately 2% of all colorectal cancer (CRC) cases and is the most common hereditary CRC syndrome.

Synopsis

 tumoral predisposition

• colorectal adenocarcinoma
• gastric carcinomas
• endometrial carcinoma (#15823135#)
• cutaneous tumors
  • sebaceous tumors (Muir-Torre syndrome)

 cerebral tumors

• astrocytomas
• gangliogliomas

Etiology

 MSH2 mutations
 MLH1 mutations
 MSH6 mutations

MSH2 and MLH1 mutations are found in approximately two-thirds of the Amsterdam-criteria-positive families and in much lower percentages of the Amsterdam-criteria-negative families.

In one series, 92%Amsterdam-criteria-positive families and 70% of the Amsterdam-criteria-negative families, a mutation was detected in one of three MMR genes: MSH2, MLH1, MSH6. 27% of the mutations were genomic rearrangements. (#12658575#)

References

 Umar A, Risinger JI, Hawk ET, Barrett JC. Testing guidelines for hereditary non-polyposis colorectal cancer. Nat Rev Cancer. 2004 Feb;4(2):153-8. PMID: #14964310#

 Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med. 2003 Mar 6;348(10):919-32. PMID: #12621137#