Background: There is a growing awareness of family history as a risk factor for disease and the availability of genetic testing for inherited cancers continues to increase. However, effective, efficient resources for educating individuals about inherited cancer risk are lacking, especially in geographic areas that are underserved by genetics services. In particular, there is a dearth of educational resources for Hispanics on cancer genetics that are both culturally relevant and available in Spanish.
Testing for mutations in the BRCA1 and BRCA2 breast-ovarian cancer susceptibility genes has been performed in over 70,000 individuals. Like other sequence-based tests, the results can reveal a normal sequence, a clearly deleterious mutation or a sequence variant of uncertain significance (VUS), in which it is not known whether the VUS confers an increased cancer risk. VUS results are confusing and occur in approximately 12% of tests. Their adequate interpretation requires a basic understanding of genetic principles, the laboratory methods utilized and pedigree analysis.
A significant proportion of patients who pursue testing for BRCA gene alterations are of reproductive age. Many are actively engaged in decisions about family planning or will be in the future. A prime concern of this population is minimizing the impact of hereditary cancer on their children. Genetically-enhanced assisted reproductive technologies (ART), such as preimplantation genetic diagnosis (PGD), as well as prenatal diagnosis (PND) followed by consideration of selective abortion, may enable individuals and couples to avoid passing genetic mutations on to their children.
Genetic testing for BRCA1 and BRCA2 (BRCA1/2) mutations is part of routine clinical care for women with a family history of breast or ovarian cancer. However, a mutation in these genes is not identified in most women who pursue testing. Such "uninformative" results do not rule out the possibility of an inherited susceptibility to these cancers. The absolute risks for breast and ovarian cancer are heterogeneous and must be estimated based upon an analysis of the family pedigree.
In 2009, 192,370 new cases of female breast cancer (BC) were diagnosed in the U.S. Of these cases, 5%- 10% were attributed to BRCA mutations. This translates to approximately 9,000 to 18,000 high-risk women who may be impacted by hereditary BC. In a given year, the number of high-risk BC patients is similar to or greater than the total number of cases of other cancers in women (e.g., oral cancer, n=10,480; stomach cancer, n=8,310; cervical cancer n=11,720; myeloma n=8,900).
Dr. Korngiebel's long-term goal is to become an independent researcher at the intersection of bioethics, informatics, and genetic testing. To work toward this goal, she will receive rigorous training that includes 11 courses supplemented by directed tutorials in order to complement her qualitative research skills with proficiency in genetics-related bioethics, informatics pertaining to Electronic Medical Record Health Information Technology, and quantitative data analysis. The research project will allow her to apply the knowledge gained through formal instruction.
The potential benefits and harms of returning genomic results to children and their parents are matters of enduring controversy--especially genomic results for adult-onset conditions that are not medically actionable in childhood. Returning results for adult-onset conditions can spur life-saving preventive measures in the parents of affected children. However, there has been long-standing concern that children who receive a result for an adult-onset condition might experience negative psychosocial outcomes such as distress or altered family functioning.
Project Narrative The potential benefits and harms of returning genomic results to children and their parents are matters of enduring controversy?especially genomic results for adult-onset conditions that are not medically actionable in childhood. Empirical data to support either position in this controversy are, however, lacking.