Somatic Mosaicism for Cancer Predisposition Genes and Pancreatic Cancer
Abstract
For some people, cancer is known to arise when a mutant gene is inherited from a parent or when the individual has been exposed to a cancer-causing agent such as tobacco smoke. However, the reason why some people develop cancer, particularly young adults, when they do not have a family history or environmental exposure is unknown. The goal of this project is therefore to determine one reason for why this happens, a process called somatic mosaicism. In human development, once an egg is fertilized it undergoes millions upon millions of cell divisions to create a fully formed human being. With every cell division there is a chance that the genetic material being duplicated to make a new cell develops an error (similar to a misspelling in a sentence that is being written over and over). The vast majority of these errors do not harm the cell nor do they interfere with growth into an adult. However, should an error occur in a cancer-causing gene that is most often the cause of inherited cancer (called a germline mutation when inherited from a parent), with time that cell may divide and initiate a cancer in the tissue it arose in during fetal development. This process is the basis of somatic mosaicism because only some cells in an individual s body contain the mutant gene and others do not. The significance of somatic mosaicism is that it cannot be detected by routine methods used to assess for inherited cancer causing genes, yet the risk of the patient developing cancer may be just as high as if the gene was inherited. Understanding if somatic mosaicism is a cause of early onset pancreatic cancer will help patients families because it means they may not have a greater risk of developing the disease themselves. It will also help patients with pancreatic cancer who have surgery to remove a tumor because it may mean the remaining pancreas is at risk for developing a second cancer, and thus the entire pancreas should be removed to lower their risk of a second pancreatic tumor. Finally, it can help improve screening methods for any person who does not have a family history of pancreatic cancer so that the disease is identified at an early, curative stage. Given that pancreatic cancer has been identified as a military focus area, our findings have the potential to have a long-term and far-reaching impact for understanding pancreatic cancer risk for service members and by extension their families. Specifically, we believe somatic mosaicism may provide an alternative and more probable explanation for cancers occurring in young men and women currently serving or having served in the military as opposed to a presumed result of a military occupational exposure.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610271
Entities
People
- Christine A Iacobuzio-Donahue
Organizations
- Memorial Sloan Kettering Cancer Center
- United States Army