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.

Public Health Relevance

Although previous studies support a beneficial role of calcium in colorectal carcinogenesis, the Institute of Medicine considers the current evidence insufficient to suggest a benefit of calcium for colorectal cancer prevention and has called for more targeted research. 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 colorectal cancer. Its results could reveal new prognostic markers and biological mechanisms, inform future dietary guidelines to lower the risk of colorectal cancer, and offer new insights for improving survival among the 1.2 million people in the US who are afflicted by this deadly disease.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Academic/Teacher Award (ATA) (K07)
Project #
5K07CA188126-03
Application #
9306074
Study Section
Subcommittee I - Transistion to Independence (NCI)
Program Officer
Perkins, Susan N
Project Start
2015-07-01
Project End
2019-06-30
Budget Start
2017-07-01
Budget End
2018-06-30
Support Year
3
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Kosumi, Keisuke; Hamada, Tsuyoshi; Koh, Hideo et al. (2018) The Amount of Bifidobacterium Genus in Colorectal Carcinoma Tissue in Relation to Tumor Characteristics and Clinical Outcome. Am J Pathol 188:2839-2852
Petrick, Jessica L; Campbell, Peter T; Koshiol, Jill et al. (2018) Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project. Br J Cancer 118:1005-1012
Liu, Li; Tabung, Fred K; Zhang, Xuehong et al. (2018) Diets That Promote Colon Inflammation Associate With Risk of Colorectal Carcinomas That Contain Fusobacterium nucleatum. Clin Gastroenterol Hepatol 16:1622-1631.e3
Yang, Wanshui; Liu, Li; Masugi, Yohei et al. (2018) Calcium intake and risk of colorectal cancer according to expression status of calcium-sensing receptor (CASR). Gut 67:1475-1483
Van Dyke, Alison L; Langhamer, Margaret S; Zhu, Bin et al. (2018) Family History of Cancer and Risk of Biliary Tract Cancers: Results from the Biliary Tract Cancers Pooling Project. Cancer Epidemiol Biomarkers Prev 27:348-351
Hamada, Tsuyoshi; Liu, Li; Nowak, Jonathan A et al. (2018) Vitamin D status after colorectal cancer diagnosis and patient survival according to immune response to tumour. Eur J Cancer 103:98-107
Trudel-Fitzgerald, Claudia; Zhou, Eric S; Poole, Elizabeth M et al. (2018) Sleep and survival among women with breast cancer: 30 years of follow-up within the Nurses' Health Study. Br J Cancer 118:e6
Simon, Tracey G; King, Lindsay Y; Chong, Dawn Q et al. (2018) Diabetes, metabolic comorbidities, and risk of hepatocellular carcinoma: Results from two prospective cohort studies. Hepatology 67:1797-1806
Hamada, Tsuyoshi; Zhang, Xuehong; Mima, Kosuke et al. (2018) Fusobacterium nucleatum in Colorectal Cancer Relates to Immune Response Differentially by Tumor Microsatellite Instability Status. Cancer Immunol Res 6:1327-1336
Momen-Heravi, Fatemeh; Masugi, Yohei; Qian, Zhi Rong et al. (2017) Tumor expression of calcium sensing receptor and colorectal cancer survival: Results from the nurses' health study and health professionals follow-up study. Int J Cancer 141:2471-2479

Showing the most recent 10 out of 23 publications