Relatively little is known about the dietary and lifestyle factors that influence survival after a diagnosis of colorectal cancer. In fact, a consensus panel of the American Cancer Society recommended, """"""""Properly conducted studies of the effect of nutrition and physical activity on the prognosis of cancer survivors are urgently needed, and should be a high priority for all academic and research funding agencies."""""""" Many of the nutritional and lifestyle factors that are thought to influence colorectal cancer progression (low vitamin D, high insulin, obesity, and physical inactivity) may operate through the vitamin D, inflammatory, and energy balance pathways in the cell. Elucidating the biological explanation for the link between these factors and colorectal cancer would enhance the acceptability of nutrition and exercise as critical for cancer treatment. To address this problem, the current proposal focuses on the investigation of biochemical, genetic, and dietary predictors of colorectal cancer recurrence and survival, with the ultimate goal of reducing mortality. Three inter-related pathways will be studied.
For Aim 1, we will examine plasma levels of vitamin D, a vitamin D prediction score, and genetic variation within the pathway, and how these exposures interact with specific molecular alterations.
For Aim 2, we will investigate plasma markers of inflammation and genetic variation in inflammation-related genes, in an effort to better understand the link between chronic inflammation and colorectal cancer. In addition, we will explore the interaction between these inflammatory markers and the vitamin D pathway.
For Aim 3, we will examine a novel dietary index that estimates long-term systemic insulin exposure, as well as the relationship between members of the insulin-like growth factor pathway and vitamin D. A major strength of this proposal is the ability to examine these plasma, genetic, and dietary factors prospectively, using three large cohorts of colorectal cancer patients with repeated dietary and lifestyle assessments;archived blood, tumor, and DNA specimens;and comprehensive data on prognostic factors and cancer outcomes. By examining these aims, this project will improve the understanding of the mechanisms that underlie colorectal cancer pathogenesis and define practical treatment measures for this difficult disease. Moreover, the current proposal will allow the candidate to gain advanced skills in biostatistics and epidemiology, pursue a focused program in colorectal cancer research, and receive close, long-term mentorship from experienced and successful investigators, promoting her transition to an independent academic researcher. The intense collaboration and vast resources of the Dana-Farber/Harvard Cancer Center, Channing Laboratory, and Harvard School of Public Health provide an ideal environment for the candidate to receive the training and mentorship needed to become a leader in the field of cancer research.

Public Health Relevance

Although colorectal cancer is the second leading cause of cancer death in the United States, relatively little is known about the dietary and lifestyle factors that influence cancer survival. Many of these modifiable factors may operate through the vitamin D, inflammatory, and energy balance pathways in the cell. The current proposal hopes to advance the understanding of colorectal cancer pathogenesis by examining potential biochemical, genetic, and dietary predictors of outcome in these pathways, with the ultimate goal of optimizing treatment strategies and improving prognosis in patients with this lethal disease.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Academic/Teacher Award (ATA) (K07)
Project #
5K07CA148894-02
Application #
8304206
Study Section
Subcommittee G - Education (NCI)
Program Officer
Perkins, Susan N
Project Start
2011-07-19
Project End
2016-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
2
Fiscal Year
2012
Total Cost
$177,828
Indirect Cost
$12,828
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
076580745
City
Boston
State
MA
Country
United States
Zip Code
02215
Fadelu, Temidayo; Zhang, Sui; Niedzwiecki, Donna et al. (2018) Nut Consumption and Survival in Patients With Stage III Colon Cancer: Results From CALGB 89803 (Alliance). J Clin Oncol 36:1112-1120
Qian, Zhi Rong; Rubinson, Douglas A; Nowak, Jonathan A et al. (2018) Association of Alterations in Main Driver Genes With Outcomes of Patients With Resected Pancreatic Ductal Adenocarcinoma. JAMA Oncol 4:e173420
Guercio, Brendan J; Zhang, Sui; Niedzwiecki, Donna et al. (2018) Associations of artificially sweetened beverage intake with disease recurrence and mortality in stage III colon cancer: Results from CALGB 89803 (Alliance). PLoS One 13:e0199244
Bullman, Susan; Pedamallu, Chandra S; Sicinska, Ewa et al. (2017) Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Science 358:1443-1448
Yurgelun, Matthew B; Kulke, Matthew H; Fuchs, Charles S et al. (2017) Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer. J Clin Oncol 35:1086-1095
Keum, NaNa; Yuan, Chen; Nishihara, Reiko et al. (2017) Dietary glycemic and insulin scores and colorectal cancer survival by tumor molecular biomarkers. Int J Cancer 140:2648-2656
Morales-Oyarvide, Vicente; Rubinson, Douglas A; Dunne, Richard F et al. (2017) Lymph node metastases in resected pancreatic ductal adenocarcinoma: predictors of disease recurrence and survival. Br J Cancer 117:1874-1882
Yuan, Chen; Bao, Ying; Sato, Kaori et al. (2017) Influence of dietary insulin scores on survival in colorectal cancer patients. Br J Cancer 117:1079-1087
Song, Mingyang; Nishihara, Reiko; Wang, Molin et al. (2016) Plasma 25-hydroxyvitamin D and colorectal cancer risk according to tumour immunity status. Gut 65:296-304
Giannakis, Marios; Mu, Xinmeng Jasmine; Shukla, Sachet A et al. (2016) Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma. Cell Rep 15:857-865

Showing the most recent 10 out of 48 publications