Calcium and Colorectal Cancer: Gene-Environment Interactions and Molecular Pathways



 DESCRIPTION (provided by applicant): Despite the increasing use of colonoscopy and improved treatment, colorectal cancer (CRC) remains the third most common cancer and cancer-related death in both US men and women. My long-term career goal is to become an independent academic investigator with the ability to apply molecular pathological epidemiology and genetic epidemiology methods to develop new prevention and control strategies for CRC. I aspire to bridge the associations observed in epidemiological work with CRC etiology and prognosis, thereby illuminating new biological mechanisms and, ultimately, decreasing CRC incidence and mortality. To achieve this goal, this K07 award will enable me to receive new training in molecular pathological epidemiology, tumor tissue collection and usage, cancer survivorship, as well as genetic epidemiology methods. The training will include mentored research, primary tumor tissue data collection, pathology laboratory internship, involvement in establishing a multi-center cancer survivor cohort, didactic coursework, publication of my research in peer- reviewed journals, attendance at scientific meetings, and submission of an R01 grant. The proposed research addresses three critical gaps in knowledge regarding the role of calcium in CRC etiology and prognosis: the etiologic heterogeneity of CRC sub-types (Aim 1), gene-environment interaction on CRC risk (Aim 2), and prognostic implications for CRC survival (Aim 3). To address these gaps, I propose a novel and integrated approach that will leverage four unique and rich population-based studies: the Nurses' Health Study, Nurses' Health Study II, Health Professionals Follow-Up Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). This study will be the largest to examine the role of calcium in combination with tumor pathological markers and genetic variants on the etiology and prognosis of CRC. Its findings could have significant etiologic and clinical implications, including 1) revealing new prognostic markers and biological mechanisms; 2) informing future dietary guidelines to lower the risk of CRC; and 3) offering new insights for improving survival among the 1.2 million people in the US who are afflicted by this deadly disease. This training and research is supported by a group of experienced mentors at Harvard. Dr. Edward Giovannucci will supervise all aspects of the training and research. I will obtain new training in molecular pathological epidemiology with Dr. Shuji Ogino, cancer survivorship with Dr. Charles Fuchs, and genetic epidemiology methods with Dr. Peter Kraft. I also have a pledge of collaboration from Drs. Donna Spiegelman at Harvard and Ulrike Peters at the Fred Hutchinson Cancer Research Center. At the completion of the award, I am confident to achieve research independence and significantly enhance my ability to contribute to the field of CRC epidemiology in innovative and important ways.