In this Project, we propose to continue the investigation of potentially modifiable nutritional and hormonal risk factors for colorectal cancer, including those that affect survival after the diagnosis of this cancer. This work will use the stored blood and urine samples, archived DNA, repeated questionnaires, and long follow-up in the Nurses'Health Study (1976-2012 with approximately 2,220 incident colorectal cancers), and tumor characteristics using pathology blocks from approximately 1,554 colorectal cancers. We propose to examine 4 inter-related pathways for colorectal cancer: vitamin D, energy balance, inflammation, and melatonin.
For aim 1, we propose to examine vitamin D status in relation to hypothesized tumor characteristics, and if preventive actions can be taken through vitamin D supplementation, particularly for women with elevated levels of plasma inflammatory factors.
For aim 2, we will examine a comprehensive dietary measure of insulin response (dietary insulin index), clarify the joint and independent effects of adiponectin, and hyperinsulinemia, and identify genes involved in obesity-mediated colon cancer.
For aim 3, we propose to better define aspirin chemoprevention of colorectal neoplasia based on COX-2 expression in the incident adenoma, to extend our work to inflammatory markers, and identify genes involved in aspirin-mediated chemoprevention. We will additionally examine the independent effect of these factors on survival following a resection of colorectal cancer. To accomplish this, we propose to link genetic alterations, modifiable factors, and hypothesized pathogenic mechanisms. This Project shares common biological and mechanistic themes with Projects 2, and 3, including the role of vitamin D, and energy balance in relation to cancer incidence and survival, and interacts closely with Project 4 for methodological issues. It also shares with the other Projects a strong scientific and administrative infrastructure provided by Cores A (cohort follow-up and data base maintenance), B (confirmation of cancer and cause of death), C (management of the biospecimens) and D (leadership and data analysis). The findings should enhance understanding of the etiology of colorectal cancer and aid in efforts to reduce incidence and death from this disease.

Public Health Relevance

We propose to identify additional nutritional, genetic and hormonal risk factors for colorectal cancer incidence and survival. We will continue to follow the 121,700 women in the Nurses'Health Study, who since 1976 have provided detailed information on lifestyle and disease diagnoses;many also provided blood and urine samples. Our findings should provide additional information on ways to reduce suffering and death due to colorectal cancer...

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA087969-15
Application #
8662724
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
15
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02115
Rice, Megan S; Rosner, Bernard A; Tamimi, Rulla M (2017) Percent mammographic density prediction: development of a model in the nurses' health studies. Cancer Causes Control 28:677-684
Hanyuda, Akiko; Cao, Yin; Hamada, Tsuyoshi et al. (2017) Body mass index and risk of colorectal carcinoma subtypes classified by tumor differentiation status. Eur J Epidemiol 32:393-407
Irshad, Humayun; Oh, Eun-Yeong; Schmolze, Daniel et al. (2017) Crowdsourcing scoring of immunohistochemistry images: Evaluating Performance of the Crowd and an Automated Computational Method. Sci Rep 7:43286
Jiménez, M C (2017) Response to comment on plasma uric acid and risk of ischaemic stroke in women. Eur J Neurol 24:e2
Wang, Tiange; Huang, Tao; Heianza, Yoriko et al. (2017) Genetic Susceptibility, Change in Physical Activity, and Long-term Weight Gain. Diabetes 66:2704-2712
Rice, Megan S; Tworoger, Shelley S; Hankinson, Susan E et al. (2017) Breast cancer risk prediction: an update to the Rosner-Colditz breast cancer incidence model. Breast Cancer Res Treat 166:227-240
Linos, E; Li, W Q; Han, J et al. (2017) Lifetime ultraviolet radiation exposure and lentigo maligna melanoma. Br J Dermatol 176:1666-1668
Nimptsch, Katharina; Song, Mingyang; Aleksandrova, Krasimira et al. (2017) Genetic variation in the ADIPOQ gene, adiponectin concentrations and risk of colorectal cancer: a Mendelian Randomization analysis using data from three large cohort studies. Eur J Epidemiol 32:419-430
Masugi, Yohei; Nishihara, Reiko; Hamada, Tsuyoshi et al. (2017) Tumor PDCD1LG2 (PD-L2) Expression and the Lymphocytic Reaction to Colorectal Cancer. Cancer Immunol Res 5:1046-1055
Simon, Tracey G; King, Lindsay Y; Chong, Dawn Q et al. (2017) Diabetes, Metabolic Comorbidities and Risk of Hepatocellular Carcinoma: Results from Two Prospective Cohort Studies. Hepatology :

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