Hereditary non-polyposis colorectal cancer

Lynch, H. M., Sinyrk, 1. C., Watson, R, Lanspa, I5 J.. Lynch, J. E. Lynch. R M-. Cavalieri, R. ].. and Boland, C R. 1993. Genetics, natural history, tumor spectrum, and pathology of hereditary non polyposis colorectal cancer An updated review. ( d.sfroe)itero/tigv 104 1535-1549. 

Hereditary non-polyposis colorectal cancer (HNPCC) is due to defects in mismatch repair (MMR) and thus to deficiencies in removing nucleotides mi-spaired by DNA polymerases as well as insertion/deletion loops (1-10 bases). This dramatically increases the mutation rate. The affected genes are MLHl (60%),MSH2 and MSH6. 

Muller, A., and R. Fishel. 2002. Mismatch repair and the hereditary non-polyposis colorectal cancer syndrome (HNPCC). Cancer Invest. 20 102-109. 

The protein products of these genes play roles in DNA repair, recombination, and regulation of transcription. A second example, HNPCC (hereditary non-polyposis colorectal cancer), was previously introduced in Chapter 13. It results from inherited mutations in enzymes involved in the DNA mismatch repair system. 

Mismatched bases produced during DNA replication are those not conforming to or A=T base pairing. They are identified and corrected in the new strand by the mismatch-repair enzyme complex . The mismatched nucleotides are identified and excised, and the gap filled by DNA polymerase. Mutations in this complex result in failure to correct mismatched base pairs and cause hereditary non-polyposis colorectal cancer (HNPCC). 

Umar A, Risinger Jl, Hawk ET, Barrett JC (2004) Testing guidelines for hereditary non-polyposis colorectal cancer. Nat Rev Cancer 4 153-158... 

There are two major forms of heredifary susceptibility to colon cancer. Familial adenomatous polyposis is caused by defects in the ARC gene (see Chapter 32). The more common hereditary non-pol3rposis colorectal cancer (HNPCC), which includes many endometrial, stomach, and urinary tract tumors, results from defects in DNA mismatch repair. )) The proteins hMSH2 and hMSLl are homologs of the E.coli MutS and MutL (main text). 

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