Hereditary nonpolyposis colorectal cancer (HNPCC) is often associated with constitutional mutations in a class of genes involved in DNA mismatch repair.
Scientists from Italy have identified 32 kindreds with germline mutations in 1 of 3 genes hMSH2, hMLH1 or hMSH6.
In this study, the scientists evaluated how many high-risk individuals in each family underwent genetic testing. They also assessed how many mutation-positive unaffected individuals accepted colonoscopic surveillance and recommended follow-up.
The team identified affected families using a population-based registry, as well as those referred from other centers.
They invited the family members to an education session with 2 members of staff.
|66% did not undergo genetic testing.|
|British Journal of Cancer|
When a kindred was consistent with HNPCC, the scientists examined neoplastic tissues for microsatellite instability (MSI) and immunohistochemical expression of MSH2, MLH1 and MSH6 proteins.
In addition, constitutional mutations were searched by SSCP or direct sequencing of the whole genomic region.
The team found that of the 164 subjects assessed by genetic testing, 89 were gene carriers. Of these 66 had a HNPCC-related cancer diagnosis and 23 remained unaffected.
The team found that 78% of the unaffected gene carriers underwent colonoscopy.
There were 292 first degree relatives at risk of cancer. Of these, 66% did not undergo genetic testing.
The team determined that this was due to difficulty in reaching "at risk" family members at risk, lack of collaboration, and lack of interest in preventive medicine.
The scientists established that the number of colorectal lesions detected at endoscopy in gene carriers was significantly higher than in controls.
Dr Ponz de Leon's team concluded, "A large fraction of high-risk individuals in mutation-positive HNPCC families does not undergo genetic testing, despite the benefits of molecular screening and endoscopic surveillance".
"This clearly indicates that there are still barriers to genetic testing in HNPCC, and that we are unable to provide adequate protection against cancer development in these families".