Accelerating Transdisciplinary Epidemiology of Colorectal Cancer Summary Tumor evolution is a heterogeneous process influenced by somatic molecular alterations, host immunity, diet, lifestyle, microbiota, and environment. Thus, I plan to take a transdisciplinary approach integrating molecular- level research, population-level study design, and assessment of environment, diet and lifestyle, utilizing my unique interdisciplinary expertise. I have been developing the transdisciplinary field of Molecular Pathological Epidemiology (MPE) with integrated strengths of both pathology and epidemiology. I will pursue two interconnecting synergistic Themes: (1) MPE of colorectal cancer (CRC) and (2) accelerating transdisciplinary epidemiology. In Theme 1, I will integrate tumor molecular and immunity analyses in 2,500 CRCs in the Nurses' Health Study (NHS), the NHS2 and the Health Professionals Follow-up Study (HPFS). I have successfully built an unprecedented high-dimensional CRC database on long-term exposures, tumor pathology, microbial, molecular and immunity data, and clinical outcome, to test the following broad-term hypotheses: (1.1) Dietary, lifestyle, environmental and genetic factors influence CRC incidence differentially by molecular, microbial and immunity subtypes. (1.2) CRC molecular features influence immune response to CRC. (1.3) CRC molecular and immunity status influences patient survival and response to drugs or modifiable dietary, lifestyle or environmental factors. (1.4) The degree of CRC intratumor heterogeneity is associated with worse prognosis and specific epidemiologic, clinical, and pathological features. We will extend our integrative research to various other settings to replicate findings and assess potential effect modifications by ethnic, socioeconomic and other factors. This project may identify potential strategies to target molecular alterations, immunity and microbiota for CRC prevention and therapy. My Theme 2 plans are; (2.1) to develop research frameworks, analysis designs and statistical methods, to address molecular and etiologic heterogeneity of cancer; (2.2) to grow the ongoing International MPE Meeting Series, to facilitate seamless transdisciplinary integration with a goal of making the STROBE-MPE guidelines; and (2.3) to synergize with experts and build new integrative transdisciplinary models, causal inference-MPE and MPE-health communication research. Thus, I aim to promote transdisciplinary integration of molecular pathology and population cancer science, and to address a critical unmet need to integrate analyses of cancer immunity, tumor molecular profiles (including microbiota and intratumor heterogeneity), modifiable exposures, genetics, and CRC incidence and death. I also try to address challenges in transdisciplinary epidemiology, including paucity of interdisciplinary experts and training programs, as well as lack of research guidelines in MPE. My unique qualifications and transdisciplinary research program can not only provide new insights on CRC etiologies in a population-based scale, but also develop novel methods / frameworks, and frontiers of population cancer science. As such, my proposed research will likely have major impacts on future research, clinical practice and public health.

Public Health Relevance

I plan to conduct Molecular Pathological Epidemiology (MPE) research on colorectal cancer (CRC) tumor characteristics, to gain insights into the role of environmental, diet, lifestyle, medical, screening and genetic factors in CRC incidence, mortality and clinical outcome. I will primarily utilize the resources of the Nurses' Health Study (NHS), the Nurses' Health Study II (NHS2), and the Health Professionals Follow-up Study (HPFS). I will also accelerate the field of transdisciplinary epidemiology with the goal of advancing several fronts of population cancer sciences to reduce suffering and death from cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Unknown (R35)
Project #
1R35CA197735-01
Application #
8955856
Study Section
Special Emphasis Panel (ZCA1-GRB-I (M1))
Program Officer
Lam, Tram K
Project Start
2015-08-10
Project End
2022-07-31
Budget Start
2015-08-10
Budget End
2016-07-31
Support Year
1
Fiscal Year
2015
Total Cost
$873,481
Indirect Cost
$275,248
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
076580745
City
Boston
State
MA
Country
United States
Zip Code
02215
Giannakis, Marios; Mu, Xinmeng Jasmine; Shukla, Sachet A et al. (2016) Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma. Cell Rep :
Cao, Yin; Nishihara, Reiko; Qian, Zhi Rong et al. (2016) Regular Aspirin Use Associates With Lower Risk of Colorectal Cancers With Low Numbers of Tumor-Infiltrating Lymphocytes. Gastroenterology 151:879-892.e4
Hanyuda, Akiko; Kim, Sun A; Martinez-Fernandez, Alejandro et al. (2016) Survival Benefit of Exercise Differs by Tumor IRS1 Expression Status in Colorectal Cancer. Ann Surg Oncol 23:908-17
Ogino, Shuji; Nishihara, Reiko (2016) All Biomedical and Health Science Researchers, Including Laboratory Physicians and Scientists, Need Adequate Education and Training in Study Design and Statistics. Clin Chem 62:1039-40
Garcia-Albeniz, Xabier; Rudolph, Anja; Hutter, Carolyn et al. (2016) CYP24A1 variant modifies the association between use of oestrogen plus progestogen therapy and colorectal cancer risk. Br J Cancer 114:221-9
Esfahani, Shadi A; Heidari, Pedram; Kim, Sun A et al. (2016) Optical Imaging of Mesenchymal Epithelial Transition Factor (MET) for Enhanced Detection and Characterization of Primary and Metastatic Hepatic Tumors. Theranostics 6:2028-2038
Song, Mingyang; Hu, Frank B; Spiegelman, Donna et al. (2016) Long-term status and change of body fat distribution, and risk of colorectal cancer: a prospective cohort study. Int J Epidemiol 45:871-83
Song, Mingyang; Nishihara, Reiko; Cao, Yin et al. (2016) Marine ω-3 Polyunsaturated Fatty Acid Intake and Risk of Colorectal Cancer Characterized by Tumor-Infiltrating T Cells. JAMA Oncol 2:1197-206
Song, Mingyang; Mehta, Raaj S; Wu, Kana et al. (2016) Plasma Inflammatory Markers and Risk of Advanced Colorectal Adenoma in Women. Cancer Prev Res (Phila) 9:27-34
McCleary, Nadine J; Sato, Kaori; Nishihara, Reiko et al. (2016) Prognostic Utility of Molecular Factors by Age at Diagnosis of Colorectal Cancer. Clin Cancer Res 22:1489-98

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