Is there a way to test for the cancer syndrome?
Hereditary nonpolyposis colorectal cancer
Genetic testing for mutations in DNA mismatch repair genes is expensive and time-consuming, so researchers have proposed techniques for identifying cancer patients who are most likely to be HNPCC carriers as ideal candidates for genetic testing. The Amsterdam Criteria (see below) are useful, but do not identify up to 30% of potential Lynch syndrome carriers. In colon cancer patients, pathologists can measure microsatellite instability in colon tumor specimens, which is a surrogate marker for DNA mismatch repair gene dysfunction. If there is microsatellite instability identified, there is a higher likelihood for a Lynch syndrome diagnosis. Recently, researchers combined microsatellite instability (MSI) profiling and immunohistochemistry testing for DNA mismatch repair gene expression and identified an extra 32% of Lynch syndrome carriers who would have been missed on MSI profiling alone. Currently, this combined immunohistochemistry and MSI profiling strategy is the most advanced way of identifying candidates for genetic testing for Lynch syndrome.
Frederick Pei Li
Molecular Epidemiology of Hereditary Cancers
In his bio on the Harvard T.H. Chan School of Public Health website, Dr. Li said about his interests and work that "recent data have established that the basic molecular defects in cancer are genetic changes that result in loss of normal cellular control mechanisms. Some of these mutations can be inherited through the germline. I have been studying inherited susceptibility of cancer through affected families. The goal is to identify genes that are involved in cancer development. I was attracted to studies of cancer families because epidemiological studies show that virtually all cancers manifest a tendency to aggregate in families. Close relatives of a cancer patient are at increased risk of that neoplasm, and perhaps other forms of cancer. The excess site-specific cancer risk is exceptionally high for carriers of certain cancer genes, in whom the attack rate can approach 100 percent. In candidate cancer families, the possibility that clustering is on the basis of chance must be excluded through epidemiological studies that establish the presence of an excess cancer risk. Predisposed families are candidates for laboratory studies to identify the inherited susceptibility factors. These investigations have led to the identification and isolation of human cancer genes, the tumor suppressor genes. These cancer genes are among more than 200 single-gene traits associated with the development of cancer. Approximately a dozen inherited susceptibility genes have been definitively identified, and many more are being sought. From studies of retinoblastoma and other rare cancers, important new information was generated about the fundamental biology of cancers that arise in many patients. Isolation of an inherited cancer susceptibility gene provides opportunities for presymptomatic testing of at-risk relatives. However, testing of healthy individuals also raise important issues regarding informed consent, confidentiality and potential for adverse psychological, social and economic effects...My colleagues and I are using families with inherited mutations in the p53 gene, which predisposes to breast cancer and diverse childhood cancers, as a model for developing a genetic testing program."