My long-term career goal is to become an independent investigator with the ability to apply molecular epidemiology methods, in the context of translational research, to gain better understanding of the factors and mechanisms related to lymphoma risk and prognosis. Recent literature reports a potential impact of vitamin D on improved prognosis in colorectal cancer, multiple myeloma, breast cancer, and most recently diffuse large B cell lymphoma (DLBCL) and chronic lymphocytic leukemia (CLL), two of the most prevalent non-Hodgkin lymphoma (NHL) subtypes. Building on my prior work on vitamin D and lymphoma etiology and these promising findings, I plan to further evaluate the role of vitamin D in lymphoma prognosis, with a focus on the two most common NHL subtypes, DLBCL and follicular lymphoma (FL). We propose to: 1) determine whether sun exposure, dietary vitamin D intake, and vitamin D related germline variations are associated with DLBCL prognosis;2) evaluate whether pre-treatment circulating vitamin D (serum 25(OH)D) is associated with FL prognosis;and 3) correlate levels of serum 25(OH)D with levels of cell cycle regulation and apoptosis protein markers within paired DLBCL and FL tumor samples. I have designed a career development training curriculum and tailored my research plan to obtain: 1) specialized didactic training in molecular epidemiology methods;2) practical experience in innovative translational research hypothesis generation, project design, relevant statistical analysis, and communication of results;3) development of leadership and management skills necessary to run a successful and effective research team;and 4) enhanced understanding of clinical and therapeutic aspects of lymphoma. To accomplish the proposed research aims, I have established a collaboration between the University of Rochester (UR) Lymphoma SPORE and the University of Iowa/Mayo Clinic (UI/MC) Lymphoma SPORE, and have secured access to a large cohort of DLBCL patients in the UI/MC Lymphoma SPORE's ongoing Molecular Epidemiology Resource. Furthermore, I have established a collaboration with the Southwest Oncology Group to access a cohort of uniformly treated FL patients for Aim 2, and we will be able to address Aim 3 within the UR Lymphoma SPORE Tissue Repository. Implementation of this plan and progress towards my goals will be monitored regularly throughout the duration of the proposed project period by a team of four experienced investigators (Jonathan Friedberg, primary mentor, clinical expertise;James Cerhan, co-mentor, molecular and genetic epidemiology expertise;Steve Bernstein, co-mentor, lymphoma biology expertise;and Derick Peterson, co-mentor, biostatistics expertise), selected specifically for their unique expertise relevant to my career development objectives and research plan. The research proposed addresses an important question, in a priority area, and promises to be a relevant contribution to the literature upon completion.
Non-Hodgkin lymphoma (NHL) is the 6th most common cancer in the United States. There are an estimated 20,000 annual NHL deaths, though epidemiology of NHL prognosis remains poorly understood. Vitamin D is a modifiable lifestyle factor, and closer evaluation of its role in NHL prognosis is warranted.