Epidemiologic and scientific research indicates that diet, lifestyle, and other modifiable factors have a significant influence on the risk of developin colorectal cancer (CRC). However, the influence of these interventions on the survival of patients with established CRC remains poorly understood. While randomized clinical trials (RCTs) demonstrate a significant survival advantage for stage III colon cancer patients who receive adjuvant fluorouracil-based chemotherapy, 35-40% of stage III patients receiving current adjuvant chemotherapy still develop cancer recurrence. Patients often seek to understand what, if any diet, lifestyle or supplement will reduce their chances of cancer recurrence. Moreover, how diet and lifestyle influence prognosis may depend, in part, on specific patient characteristics as well as molecular alterations in the tumor. We propose to address these gaps in knowledge within a NCI-sponsored, large, double-blind, placebo- controlled RCT assessing the influence of celecoxib on survival in stage III colon cancer patients who are concurrently receiving standard adjuvant chemotherapy (CALGB 80702). Beyond directly addressing the role of COX inhibition, the trial provides a) two longitudinal prospective assessments of diet, medication usage, and lifestyle habits;b) tumor specimens to examine how exogenous factors interact with specific molecular alterations;c) prospectively collected blood and germline DNA;and d) extensive data on cancer recurrence, mortality, and treated-related toxicity. Since pathologic stage, performance status, post-operative therapy and follow-up are carefully defined in this trial, residual confounding by disease and treatment characteristics should be minimized. In this application, we propose to examine the influence celecoxib and inflammation (Aim 1), and relevant effect modifying pathways (Aim 2) on the risk of cancer recurrence, mortality, and treatment-related toxicity.
Each aim extends current knowledge in these areas. Beyond the aforementioned hypotheses, this cohort will allow for the rapid examination of future hypotheses as they emerge. Ultimately, the proposed work seeks to improve our understanding of CRC biology, identify interventions that can improve patient survival, and, with the extensive clinical pathologic, genomic, and biomarker data available for analysis, inform clinicians how to maximally utilize these interventions to improve clinical care.

Public Health Relevance

While considerable evidence supports the role of diet and lifestyle on the risk of developing colorectal cancer, the effect that these factors play on the survival of patients with established colorectal cancer is largely unknown. Using the resources of a large clinical trial, we propose to define the influence of these factors on patient survival o provide valuable information on colorectal cancer biology and offer meaningful interventions to improve patient outcomes.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01CA169141-02
Application #
8737807
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Elena, Joanne W
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02215
Mima, Kosuke; Nowak, Jonathan A; Qian, Zhi Rong et al. (2016) Tumor LINE-1 methylation level and colorectal cancer location in relation to patient survival. Oncotarget :
Kim, Sun A; Inamura, Kentaro; Yamauchi, Mai et al. (2016) Loss of CDH1 (E-cadherin) expression is associated with infiltrative tumour growth and lymph node metastasis. Br J Cancer 114:199-206
Giannakis, Marios; Mu, Xinmeng Jasmine; Shukla, Sachet A et al. (2016) Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma. Cell Rep :
Kroenke, Candyce H; Neugebauer, Romain; Meyerhardt, Jeffrey et al. (2016) Analysis of Body Mass Index and Mortality in Patients With Colorectal Cancer Using Causal Diagrams. JAMA Oncol 2:1137-45
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
Keum, NaNa; Cao, Yin; Oh, Hannah et al. (2016) Sedentary behaviors and light-intensity activities in relation to colorectal cancer risk. Int J Cancer 138:2109-17
Morales-Oyarvide, Vicente; Meyerhardt, Jeffrey A; Ng, Kimmie (2016) Vitamin D and Physical Activity in Patients With Colorectal Cancer: Epidemiological Evidence and Therapeutic Implications. Cancer J 22:223-31
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
Babic, Ana; Shah, Sonali M; Song, Mingyang et al. (2016) Soluble tumour necrosis factor receptor type II and survival in colorectal cancer. Br J Cancer 114:995-1002
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

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