# Selenium Chemoprevention: Benefits and Harms

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2020 · $364,639

## Abstract

ABSTRACT
With increased interest in patient-centered outcomes research and precision medicine, investigation of
heterogeneity of treatment effect (HTE) in clinical trials has emerged as a key area of study. HTE is an
assessment of the degree to which the impact of an intervention varies between subgroups. Evidence from trials
of selenium supplementation indicates that this is a critical area for investigation of HTE. To date, three major
clinical trials of the trace element selenium (Se) as a chemopreventive agent have been completed. First, in the
Nutritional Prevention of Cancer (NPC) trial, participants were supplemented with 200 µg of Se per day or
matching placebo, and a statistically significant 58% reduction in colorectal cancer incidence among participants
randomized to receive the selenium supplement was observed. Next, the results of the Selenium and Vitamin E
Prostate Cancer Prevention Trial (SELECT) were published. The largest trial to date of Se for cancer prevention,
SELECT demonstrated no reduction in risk of colorectal cancer among men supplemented with 200 µg/d of Se
as L-selenomethionine. We have recently completed the Selenium Trial, which was the third major clinical trial
of Se for chemoprevention. This was a Phase III, randomized, double-blind, placebo-controlled clinical trial in
which 1535 participants received 200 µg/d of Se as selenized yeast or placebo to ascertain whether Se
supplementation reduced the risk of colorectal adenoma recurrence. No differences in overall colorectal
adenoma recurrence by intervention group were detected; however, subgroup analyses revealed the presence
of heterogeneity of treatment effect (HTE). Among participants who had an advanced adenoma at baseline,
there was a statistically significant reduction in adenoma recurrence for those randomized to Se as compared to
placebo. However, there was also a statistically significant increase in the incidence of type 2 diabetes (T2D)
among older participants (>63 years) receiving selenium. These results identify a major research gap regarding
the need for identification of individual characteristics that may contribute to HTE and thus determine whether
Se supplementation elicits a beneficial or harmful effect. This is a particularly timely question given that
approximately half of American adults report using dietary supplements. We propose herein to investigate
several factors that may affect individual outcomes related to Se supplementation, including 1) Genetic
background; 2) Intake and blood concentrations of fat-soluble antioxidants; and 3) Oxylipin profiles in response
to Se supplementation. In summary, we contend that the in vivo efficacy and toxicity of Se in a given individual
may be influenced by genetic background, interactions with antioxidants, and oxylipin metabolomic profiles. The
findings of this study will have a direct impact on public health recommendations by identifying individual
characteristics that may elicit either beneficial ...

## Key facts

- **NIH application ID:** 9934983
- **Project number:** 5R01CA151708-07
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** ELIZABETH T JACOBS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $364,639
- **Award type:** 5
- **Project period:** 2011-07-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934983

## Citation

> US National Institutes of Health, RePORTER application 9934983, Selenium Chemoprevention: Benefits and Harms (5R01CA151708-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9934983. Licensed CC0.

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