Why do second, independent cancers occur at higher rates in patients who have survived a primary cancer than in a cancer-naïve population?
Background: Second cancers are a major problem for cancer survivors. Grouped as a single outcome in the Surveillance Epidemiology and End Results (SEER) database, second cancers rank fourth in overall cancer incidence and are often associated with poor outcomes. However, researchers have not taken full advantage of this population to study risk factors and mechanisms. The influence of prior therapeutic interventions (including chemo- and radio-therapies) and somatic mutations in this population has been studied to some degree. However, the extent to which underlying genetic predispositions, environmental factors, and life-style behaviors influence risk remain relatively underexplored. It is likely that at least some of the contributing risk factors and mechanisms would be relevant to all cancer patients, not only those with second independent cancers.
Feasibility: Given the high risk of these developing in cancer patients and their involvement with medical oncology personnel, it should be substantially easier to monitor cancer survivors for the development of a second cancer than to observe healthy individuals for the development of a first cancer. Cancer survivors are often followed prospectively for treatment response and complications, as well as disease progression. Technologies that identify somatic alterations can be integrated with genome-wide annotation of germ-line DNA to investigate the relationship between genetic susceptibility in high-risk individuals and second cancers. With the advent of new, more efficient technologies, it is feasible to broaden these efforts to large-scale clinical trial studies. Efforts to capture clinical, epidemiological, and therapeutic data could also be centered on the development of large-scale cohorts of cancer survivors at risk for second cancers. Because of their heightened risk of cancer, this population of patients may be more motivated, and therefore well suited, for prospective prevention studies, such as chemoprevention or behavioral modifications.
Implications of success: Studying patients who have had primary cancers for the development of second cancers could help uncover pathogenic mechanisms of both cancers, including shared etiologic pathways and therapy-related risks. These insights are likely to inform new strategies for preventive interventions.