This is an application for a K07 award for Dr. Heidi Hanson, a tenure-line Assistant Professor of Surgery at the University of Utah. Dr. Hanson is establishing herself as a young investigator in genetic and environmental cancer epidemiology. Her training in sociology, demography, and life course epidemiology, experience with advance quantitative methodologies, and familiarity with the Utah Population Database perfectly poise her innovative work in this field of study. However, she is lacking the necessary training in: 1) cancer biology and pathology; 2) cutting-edge genetic epidemiology pedigree methods; 3) genomic and epigenetic tumor profiling; and 4) managing and implementing successful multidisciplinary team science. This training will allow Dr. Hanson to achieve her goal to launch an independent cancer research program focused on improving precision strategies of cancer screening and treatment methods through gene-environment scientific discoveries. Dr. Hanson has assembled a mentoring team comprising of a primary mentor, Dr. Nicola Camp, a genetic epidemiologist and nationally renowned investigator, and two co-mentors: Dr. Orly Alter, a Utah Science Technology and Research Initiative (USTAR) associate professor of bioengineering and human genetics, and Dr. Ken Smith, an internationally known expert in population-based analyses and genetic/family epidemiology. Dr. Hanson has six advisors and one contributor with expertise in urologic oncology, clinical outcomes in urologic malignancies and health services research, etiology of bladder cancer, epigenetic changes, high risk cancer studies, pathology, and environmental epidemiology. Bladder cancer (BCa) is a heterogeneous disease, with strong support for multiple subtypes, including a basal/squamous-like (BASQ) tumor subtype. However, there is a lack of consensus for the number and characteristics of additional subtypes. BCa risk may be driven by both genetic and environmental risk factors, with different etiologies yielding different subtypes of BCa. In terms of familial clustering, these different etiological factors may exhibit as different multi-cancer configurations across a spectrum of organs (tumor spectrum). Using dimension reduction techniques to perform an integrative multi-omic analysis of BCa expression and methylation combined with information on etiological factors associated with BCa risk can lead to the identification of subtypes of BCa that are epidemiologically and clinically relevant. Dr. Hanson will accomplish this through the following research specific aims: 1) Utilize dimension reduction techniques for integrative analysis of BCa multi-omics data; 2) Determine BCa dimensions associated with environmentally- driven BCa subtypes; 3) Identify BCa dimensions associated with genetically-driven BCa subtypes. This research will prepare Dr. Hanson to design and implement a novel R01 application to further investigate the multi-omic cancer profiles across a spectrum of organs and advance gene-environment research.
Familial cluster subtyping of BCa has the potential to identify and characterize: ?genetically- driven BCa subtypes?, ?environmental BCa subtypes?, or ?gene-environment BCa subtypes?. When combined with multi-omic data, familial clustering is a powerful design to parse out distinct subtypes of BCa because family members share both genes and early life environments.