Recent evidence has confirmed that positive energy balance, as estimated by obesity, strongly influences prostate carcinogenesis. However, the complexity of how energy balance influences, and is influenced, by various metabolic hormones and sympathetic nervous system activity (SNS) adds considerable complexity to the role of energy balance for this cancer. Further, the influences of energy balance may differ for prostate cancer incidence and progression. A third complicating factor is that there may be distinct etiologies for early- onset and late-onset prostate cancers. We propose three distinct patterns, suggested by our preliminary data and other studies, whereby energy balance related variables influence prostate cancer: Pattern 1: Metabolic alterations associated with obesity and lack of physical activity, including high insulin and leptin, and low adiponectin levels, increase risk of prostate cancer progression. Further, the low testosterone levels associated with obesity may contribute to more poorly differentiated cancers and thus a worse prognosis. Pattern 2: Higher insulin-like growth factor (IGF-1) levels influence progression of well- to moderately-well differentiated prostate cancers, whereas cancers that have molecular alterations in the IGF-1 signaling pathway and hence upregulated IGF-1 signaling are relatively unresponsive to circulating IGF-1 levels. Pattern 3: Younger men with an inherent metabolic phenotype related to SNS activity that disassociates high energy intake from weight gain and which is associated with chronic prostatitis/chronic pelvic pain syndrome prostatitis are at increased risk of prostate cancer. We will address these three patterns whereby energy balance may influence prostate cancer risk in the Health Professionals Follow-up Study (HPFS), a cohort of the 47,000 men free of cancer at baseline in 1986. We project 6,085 new cases of prostate cancer by 2010, including 668 fatal cases, with tumor blocks from over 1,900 prostatectomy cases. The sources of the exposure data in the HPFS are questionnaire, including diet, anthropometric measures, activity, medication use, and plasma samples. The outcome data will be based on (1) medical record and pathology report review, and (2) tissue block markers that correlate with disease progression. Stratified analysis and multivariate analysis will be used to control for confounding factors. Our ultimate goal is to better understand how body weight, and related dietary and other modifiable factors, influence prostate carginogenesis at various stages.

Public Health Relevance

Our preliminary data and other data suggest that energy balance-related variables influence prostate cancer. To help reduce the apparent inconsistencies in the literature for energy balance and prostate cancer risk, we hypothesize three distinct patterns whereby energy balance variables may influence prostate cancer risk. These three patterns would also help explain some of the apparent age patterns of prostate cancer epidemiology. We propose to study these patterns in the Health Professionals Follow-up Study (HPFS), a cohort of the 47,000 men free of cancer at baseline in 1986. We project 6,085 new cases of prostate cancer by 2010, including 668 fatal cases, with tumor blocks from over 1,900 prostatectomy cases. Our ultimate goal is to better understand how body weight, and related dietary and other modifiable factors, influence prostate carcinogenesis at various stages with a focus on prevention of morbidity and mortality from these risk factors.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA133891-05
Application #
8301690
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Mahabir, Somdat
Project Start
2008-09-26
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2014-07-31
Support Year
5
Fiscal Year
2012
Total Cost
$625,460
Indirect Cost
$158,230
Name
Harvard University
Department
Nutrition
Type
Schools of Public Health
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115
Zhang, Ran; Chomistek, Andrea K; Dimitrakoff, Jordan D et al. (2015) Physical activity and chronic prostatitis/chronic pelvic pain syndrome. Med Sci Sports Exerc 47:757-64
Markt, Sarah C; Valdimarsdottir, Unnur A; Shui, Irene M et al. (2015) Circadian clock genes and risk of fatal prostate cancer. Cancer Causes Control 26:25-33
Penney, Kathryn L; Sinnott, Jennifer A; Tyekucheva, Svitlana et al. (2015) Association of prostate cancer risk variants with gene expression in normal and tumor tissue. Cancer Epidemiol Biomarkers Prev 24:255-60
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Siddiqui, Mohummad Minhaj; Wilson, Kathryn M; Epstein, Mara M et al. (2014) Vasectomy and risk of aggressive prostate cancer: a 24-year follow-up study. J Clin Oncol 32:3033-8
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Van Blarigan, Erin L; Ma, Jing; Kenfield, Stacey A et al. (2014) Plasma antioxidants, genetic variation in SOD2, CAT, GPX1, GPX4, and prostate cancer survival. Cancer Epidemiol Biomarkers Prev 23:1037-46

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