Grant Number:	3U01CA167552-09S1 Interpret this number
Primary Investigator:	Willett, Walter
Organization:	Harvard School Of Public Health
Project Title:	Cancer Epidemiology Cohort in Male Health Professionals
Fiscal Year:	2021

Project Summary/Abstract Prostate cancer is the most common cancer and the second most common cause of cancer death in U.S. men. Over 3 million men are currently living with prostate cancer in the U.S. By 2030, the estimated prevalence is 5.6 million prostate cancer survivors. Prevalence of supplement use, often in mega-doses, is particularly high in prostate cancer survivors with estimates ranging from 20% to 60%. Although beneficial effects are not established, evidence suggest that pre-diagnostic intake of certain micronutrients taken at high doses may increase risk of developing prostate cancer. Thus, millions of men with prostate cancer are currently taking high doses of numerous supplements, despite minimal evidence of efficacy, and possibly even harm, at least based on evidence from pre-diagnostic intake. We propose a cost-efficient study, utilizing existing resources from a sub-cohort of 5,500 prostate cancer survivors in the Health Professionals Follow-up Study. Biennially updated detailed data on lifestyle, diet, prostate cancer treatments, PSA levels, clinical progression, and co-morbidities collected over a period of 30 years, will allow us to examine long- term effects (duration, latency), source (natural versus synthetic), and dose, and to determine the shape of any non-linear dose-response relationship. We will focus on dietary supplements commonly used by prostate cancer survivors, which have also been widely studied for their association with prostate cancer incidence, but lack data for survival, i.e., calcium, retinol (vitamin A), selenium, vitamin E, zinc, and marine omega-3 fatty acids. First, we will test whether independent of pre-diagnostic intake, post-diagnostic intakes of supplemental calcium, retinol, zinc, selenium, vitamin E, and omega-3 fatty acid are characterized by a J-shaped or U-shaped dose-response relationship with lethal prostate cancer, with no association or inverse associations at lower doses, and increased mortality at higher doses (Aim 1). Second, we will assess whether longer post-diagnostic duration of high-dose supplement intake is associated with higher risk of lethal prostate cancer in prostate cancer survivors (Aim 2). Considering the widespread use of dietary supplements, and the large and increasing number of prostate cancer survivors, with an estimated prevalence of 5.6 million in 2030, even a small or modest association between dietary supplements and prostate cancer prognosis will have substantial clinical and public health impact.





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