The team compared the rates of genetically defined hereditary nonpolyposis colorectal cancer (HNPCC) among individuals with early onset colorectal cancer (CRC) drawn from a high-risk clinic and a population-based cancer registry.
The findings of the study were reported in the April issue of Gastroenterology.
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.
|Predictors of MSH2 or MLH1 mutation:|
- No. colorectal cancers in family
| Gastroenterology |
A total of 43 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). The percentage with any personal or family history of another HNPCC-related cancer (70% vs 74%) was also similar.
However, 28 of 40 (70%) of the UCSF tumors were MSI-H, compared with 6 of 18 (33%) of KP tumors.
Some 13 germline MSH2 or MLH1 mutations were found in the UCSF group compared with none in the KP group.
The researchers found that, in a multivariate analysis, institution and the total number of colorectal cancers in the family were independent predictors of MSH2 or MLH1 mutation.
Dr Jonathan P. Terdiman, of the University of California, San Francisco, said on behalf of his colleagues, "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," he concluded.