Epidemiology of multiple primary cancers: Genetic susceptibility and microsatellite instability.

摘要

With prolonged average survival of cancer patients and improvement of diagnostic techniques and treatment strategies, the importance of studying the etiology and risk of multiple primary cancers has been intensified. Using age of onset of the first cancer and microsatellite instability as indicators for genetic susceptibility, this study investigated whether there is evidence for genetic components in the etiology of multiple primary cancers.; The association between age at diagnosis of first cancer and the risk of developing second cancer in patients with multiple primary cancers was evaluated using data from the Surveillance, Epidemiology, and End Results (SEER). We hypothesized that patients with suspected hereditary cancer syndromes would have an increased risk of developing a second primary cancer, compared to those whose first cancer was diagnosed after age 50. Four comparison groups of cancer types were constructed, including: (1) cancers known to aggregate in hereditary cancer syndromes, (2 )cancers with no known familial aggregation, (3) cancers with shared environmental risk factors, and (4) randomly selected pairs of tumors.; Patients who developed their first cancer before 50 years and whose multiple primaries consisted of those seen in either Hereditary Nonpolyposis Colorectal Cancer (HNPCC) syndrome, or hereditary breast-ovarian cancers, had a twofold to sevenfold higher risk of developing a second cancer compared to patients with similar tumor types but who were diagnosed after age 50. In all groups, cancer patients who developed the first cancer by age 50 have a twofold higher risk of second cancers.; The association between multiple primary cancers and genetic susceptibility as expressed by microsatellite instability was evaluated using a case-control study design, where cases were colorectal cancer patients who developed a second primary cancer, and controls were sporadic single colorectal cancer patients, frequency-matched by gender and survival.; The results of the case-control study showed that microsatellite instability (MSI) of colorectal cancers did not increase the risk of developing multiple primary cancers in general; however, it did occur more frequently in patients who developed any multiple primary cancers of the HNPCC tumor spectrum. Among controls, microsatellite instability occurred most often in younger onset colorectal cancer patients, as compared to older onset patients.; We conclude that some cancer syndromes with strong genetic components may be distinguishable using patients with multiple primaries and age at diagnosis of the first cancer. However, the power to detect this association may be related to the prevalences of hereditary cancer susceptibility genes and hereditary cancer syndromes. The presence of microsatellite instability in colorectal cancer patients increases the risk of developing the types of cancers seen in the HNPCC spectrum. However, microsatellite instability in CRC patients does not significantly increase risk of other cancers, including smoking-related cancers, breast cancer, or prostate cancer. (Abstract shortened by UMI.)