Hereditary nonpolyposis colorectal cancer in young colorectal cancer patients: high-risk clinic versus population-based registry

Gastroenterology. 2002 Apr;122(4):940-7. doi: 10.1053/gast.2002.32537.


Background & aims: Early onset colorectal cancer (CRC) is an important feature of hereditary nonpolyposis colorectal cancer (HNPCC). We sought to compare rates of genetically defined HNPCC among individuals with early onset CRC drawn from a high-risk clinic and a population-based cancer registry.

Methods: Probands with CRC diagnosed before 36 years of age were enrolled from a high-risk CRC clinic at the University of California, San Francisco (UCSF), and a population-based Kaiser Permanente (KP) Health Plan cancer registry. Probands provided cancer family histories and tumors for microsatellite instability (MSI) testing and MSH2/MLH1 protein immunostaining. Germline MSH2 and MLH1 mutational analysis was performed.

Results: Forty-three probands were enrolled from UCSF and 23 from KP. The UCSF and KP probands had similar median age of onset of CRC (30 vs. 31 years) and the percentage with any personal or family history of another HNPCC-related cancer (70% vs. 74%). However, 28 of 40 (70%) of the UCSF tumors were MSI-H compared with 6 of 18 (33%) of KP tumors (P = 0.01), and 13 germline MSH2 or MLH1 mutations were found in the UCSF group compared with 0 in the KP group (P = 0.0001). In a multivariate analysis, institution (P = 0.002) and the total number of colorectal cancers in the family (P = 0.0001) were independent predictors of MSH2 or MLH1 mutation.

Conclusions: Family history of cancer is an important feature of HNPCC, even among individuals with early onset CRC. Caution must be undertaken when extrapolating data regarding HNPCC from high-risk clinic populations to the general population.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adolescent
  • Adult
  • Age of Onset
  • Ambulatory Care Facilities
  • Carrier Proteins
  • Colorectal Neoplasms / chemistry
  • Colorectal Neoplasms / epidemiology*
  • Colorectal Neoplasms / genetics*
  • DNA Mutational Analysis
  • DNA-Binding Proteins*
  • Germ-Line Mutation
  • Humans
  • Immunohistochemistry
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / genetics
  • Nuclear Proteins
  • Predictive Value of Tests
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins / genetics
  • Registries
  • Risk Factors


  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DNA-Binding Proteins
  • MLH1 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein