While follow-up of the 121,700 women in the Nurses' Health Study (NHS) will be supported by a pending UM1 (priority score=10), this competing renewal of PO1 CA87969, Dietary and Hormonal Determinants of Cancer in Women continues the scientific pursuit of modifiable determinants of breast, colorectal, and ovarian cancers. A primary, cross-cutting theme is the role of metabolites and metabolomic signatures in the etiology and progression of these cancers, including developing novel statistical approaches. Further, gene expression analyses of tumor tissue will enable us to identify pathways linking risk factors to cancer. The repeated measures of behavioral factors (eg, diet) since 1976, with our extensive biorepository (blood, urine, tumor tissue), allows us to thoroughly examine relations between behavior, biomarkers, and tumor expression. Although NHS has limited racial minorities, we include research to compare prevalence of metabolomic signatures predicting breast cancer in healthy white vs black participants as a step to understand racial differences in incidence, and an Aim to collaborate with the VITAL trial to identify colorectal adenoma to test if vitamin D supplements may be particularly beneficial in blacks (building on previous research in this PO1 finding relations of vitamin D to adenoma). Briefly, Project 1 will test whether: specific metabolites and metabolomic signatures are associated with breast cancer risk and survival; metabolomics or gene expression patterns are etiologic factors underlying the relation of diet to breast cancer; energy balance and insulin resistance (eg, strength training, diet, metformin use) are associated with breast cancer risk and survival, including according to tumor expression. Project 2 will examine whether: metabolites/ metabolomic signatures are associated with colorectal cancer risk and survival; energy balance and insulin resistance are associated with colorectal cancer risk and survival, including according to tumor expression; how anti-inflammatory agents (eg, aspirin) reduce colorectal cancer, with extensive consideration of etiologic pathways; and supplemental vitamin D reduces colorectal adenoma in blacks and whites in a randomized trial. Project 3 will examine whether lipid metabolites and metabolomic signatures and inflammation-associated exposures are related to ovarian cancer, including according to tumor expression, and will initiate novel research into ovarian cancer survival. Project 4 will develop statistical approaches to analyzing metabolomics data, and to predicting cancer risk. In summary, these highly interrelated Projects will enhance our understanding of the etiology and progression of cancer and potential preventive strategies.

Public Health Relevance

These highly interrelated Projects integrate metabolomics, gene expression, molecular characteristics of tumors and behavioral factors to enhance our understanding of the etiology of cancer and potential preventive strategies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA087969-19
Application #
9564058
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Lai, Gabriel Y
Project Start
2000-09-12
Project End
2020-06-30
Budget Start
2018-07-01
Budget End
2019-06-30
Support Year
19
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
Li, Jun; Rice, Megan S; Huang, Tianyi et al. (2018) Circulating prolactin concentrations and risk of type 2 diabetes in US women. Diabetologia 61:2549-2560
Farvid, Maryam S; Chen, Wendy Y; Rosner, Bernard A et al. (2018) Fruit and vegetable consumption and breast cancer incidence: Repeated measures over 30 years of follow-up. Int J Cancer :
Tabung, Fred K; Wang, Weike; Fung, Teresa T et al. (2018) Association of dietary insulinemic potential and colorectal cancer risk in men and women. Am J Clin Nutr 108:363-370
O'Mara, Tracy A; Glubb, Dylan M; Amant, Frederic et al. (2018) Identification of nine new susceptibility loci for endometrial cancer. Nat Commun 9:3166
Graff, Rebecca E; Cho, Eunyoung; Preston, Mark A et al. (2018) Dietary Acrylamide Intake and Risk of Renal Cell Carcinoma in Two Large Prospective Cohorts. Cancer Epidemiol Biomarkers Prev 27:979-982
Marinac, Catherine R; Birmann, Brenda M; Lee, I-Min et al. (2018) Body mass index throughout adulthood, physical activity, and risk of multiple myeloma: a prospective analysis in three large cohorts. Br J Cancer 118:1013-1019
Zong, Geng; Valvi, Damaskini; Coull, Brent et al. (2018) Persistent organic pollutants and risk of type 2 diabetes: A prospective investigation among middle-aged women in Nurses' Health Study II. Environ Int 114:334-342
Houghton, Lauren C; Sisti, Julia S; Hankinson, Susan E et al. (2018) Estrogen Metabolism in Premenopausal Women Is Related to Early Life Body Fatness. Cancer Epidemiol Biomarkers Prev 27:585-593
Hagan, Kaitlin A; Erekson, Elisabeth; Austin, Andrea et al. (2018) A prospective study of the natural history of urinary incontinence in women. Am J Obstet Gynecol 218:502.e1-502.e8
Cook, Erin E; Gershman, Susan T; Kim, Jane J et al. (2018) Trends of two HPV-associated cancers in Massachusetts: cervical and oropharyngeal cancer. Cancer Causes Control 29:435-443

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