Holly L. Nicastro

Selenium and prostate cancer prevention: insights from the selenium and vitamin E cancer prevention trial (SELECT).

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was conducted to assess the efficacy of selenium and vitamin E alone, and in combination, on the incidence of prostate cancer. This randomized, double-blind, placebo-controlled, 2 × 2 factorial design clinical trial found that neither selenium nor vitamin E reduced the incidence of prostate cancer after seven years and that vitamin E was associated with a 17% increased risk of prostate cancer compared to placebo. The null result was surprising given the strong preclinical and clinical evidence suggesting chemopreventive activity of selenium. Potential explanations for the null findings include the agent formulation and dose, the characteristics of the cohort, and the study design. It is likely that only specific subpopulations may benefit from selenium supplementation; therefore, future studies should consider the baseline selenium status of the participants, age of the cohort, and genotype of specific selenoproteins, among other characteristics, in order to determine the activity of selenium in cancer prevention.

Garlic and Onions: Their Cancer Prevention Properties

The Allium genus includes garlic, onions, shallots, leeks, and chives. These vegetables are popular in cuisines worldwide and are valued for their potential medicinal properties. Epidemiologic studies, while limited in their abilities to assess Allium consumption, indicate some associations of Allium vegetable consumption with decreased risk of cancer, particularly cancers of the gastrointestinal tract. Limited intervention studies have been conducted to support these associations. The majority of supportive evidence on Allium vegetables cancer-preventive effects comes from mechanistic studies. These studies highlight potential mechanisms of individual sulfur-containing compounds and of various preparations and extracts of these vegetables, including decreased bioactivation of carcinogens, antimicrobial activities, and redox modification. Allium vegetables and their components have effects at each stage of carcinogenesis and affect many biologic processes that modify cancer risk. This review discusses the cancer-preventive effects of Allium vegetables, particularly garlic and onions, and their bioactive sulfur compounds and highlights research gaps. Cancer Prev Res; 8(3); 181–9. ©2015 AACR.

Preventive Effects of NSAIDs, NO-NSAIDs, and NSAIDs Plus Difluoromethylornithine in a Chemically Induced Urinary Bladder Cancer Model

Urinary bladder cancer prevention studies were performed with the nonsteroidal anti-inflammatory drugs (NSAID) naproxen (a standard NSAID with a good cardiovascular profile), sulindac, and their nitric oxide (NO) derivatives. In addition, the effects of the ornithine decarboxylase inhibitor, difluoromethylornithine (DFMO), alone or combined with a suboptimal dose of naproxen or sulindac was examined. Agents were evaluated at their human equivalent doses (HED), as well as at lower doses. In the hydroxybutyl(butyl)nitrosamine (OH-BBN) model of urinary bladder cancer, naproxen (400 or 75 ppm) and sulindac (400 ppm) reduced the incidence of large bladder cancers by 82%, 68%, and 44%, respectively, when the agents were initially given 3 months after the final dose of the carcinogen; microscopic cancers already existed. NO-naproxen was highly effective, whereas NO-sulindac was inactive. To further compare naproxen and NO-naproxen, we examined their effects on gene expression in rat livers following a 7-day exposure. Limited, but similar, gene expression changes in the liver were induced by both agents, implying that the primary effects of both are mediated by the parent NSAID. When agents were initiated 2 weeks after the last administration of OH-BBN, DFMO at 1,000 ppm had limited activity, a low dose of naproxen (75 ppm) and sulindac (150 ppm) were highly and marginally effective. Combining DFMO with suboptimal doses of naproxen had minimal effects, whereas the combination of DMFO and sulindac was more active than either agent alone. Thus, naproxen and NO-naproxen were highly effective, whereas sulindac was moderately effective in the OH-BBN model at their HEDs. Cancer Prev Res; 7(2); 246–54. ©2013 AACR.

Using 2 Assessment Methods May Better Describe Dietary Supplement Intakes in the United States

BACKGROUND One-half of US adults report using a dietary supplement. NHANES has traditionally assessed dietary supplement use via a 30-d questionnaire but in 2007 added a supplement module to the 24-h dietary recall (24HR). OBJECTIVE We compared these 2 dietary assessment methods, examined potential biases in the methods, and determined the effect that instrument choice had on estimates of prevalence of multivitamin/multimineral dietary supplement (MVMM) use. METHODS We described prevalence of dietary supplement use by age, sex, and assessment instrument in 12,285 adults in the United States (>19 y of age) from NHANES 2007-2010. RESULTS When using data from the questionnaire alone, 29.3% ± 1.0% of men and 35.5% ± 1.0% of women were users of MVMMs, whereas data from the 24HR only produced prevalence estimates of 26.3% ± 1.1% for men and 33.2% ± 1.0% for women. When using data from both instruments combined, 32.3% ± 1.2% of men and 39.5% ± 1.1% of women were classified as MVMM users. Prevalence estimates were significantly higher by 2-9% in all age-sex groups when using information from both instruments combined than when using data from either instrument individually. A digit preference bias and flattened slope phenomenon were observed in responses to the dietary supplement questionnaire. A majority (67%) of MVMMs were captured on both instruments, whereas 19% additional MVMMs were captured on the questionnaire and 14% additional on the 24HR. Of those captured only on the 24HR, 26% had missing label information, whereas only 12% and 9% of those captured on the questionnaire or both, respectively, had missing information. CONCLUSIONS Use of both the dietary supplement questionnaire and the 24HR can provide advantages to researchers over the use of a single instrument and potentially capture a larger fraction of dietary supplement users.

Nutrigenomics and Cancer Prevention.

Mounting evidence continues to point to dietary habits as a modifier of cancer risk and tumor behavior; although it is clear that considerable variability occurs across studies. While genetic public health messages can be developed, the use of mean values may result in underexposure to some essential and nonessential food components, yet precipitate overexposure to nutrients. Undeniably, inconsistencies in the literature may reflect variation in timing of exposures to specific dietary constituents, interactions with the food matrix, processing technologies, or the genomic variation among individuals, which can influence absorption, metabolism, and/or the molecular target. Interindividual variability in genetics, epigenetics, transcriptomics, proteomics, metabolomics, or microbiomics can influence the magnitude and direction of response to bioactive food components, as briefly reviewed in this article. Unquestionably, understanding nutrigenomics holds promise to reveal those who will benefit most from dietary interventions plus identify any who might be placed at risk due to overexposures.

The Accumulating Data to Optimally Predict Obesity Treatment (ADOPT) Core Measures Project: Rationale and Approach: ADOPT Core Measures Project

Individual variability in response to multiple modalities of obesity treatment is well documented, yet our understanding of why some individuals respond while others do not is limited. The etiology of this variability is multifactorial; however, at present, we lack a comprehensive evidence base to identify which factors or combination of factors influence treatment response.

Navigating the road ahead: addressing challenges for use of metabolomics in epidemiology studies

Metabolomics platforms allow for the measurement of hundreds to thousands of unique small chemical entities, as well as offer extensive coverage of metabolic markers related to obesity, diet, smoking, and other exposures of high interest to health scientists. Nevertheless, its potential use as a tool in population-based study design has not been fully explored. As the field of metabolomics continues to mature, and in part, accelerate through the National Institutes of Health (NIH) investment of ≤65 million in the Common Funds Metabolomics Program (https://common fund.nih.gov/metabolomics/index), it is time to consider those challenges most pertinent to epidemiologic studies.

The Future of Metabolomic Profiling in Population-Based Research: Opportunities and Challenges

Metabolomics is an approach that employs technologies to measure small molecule metabolites in biological samples, thus providing epidemiologists and other investigators with a means to discover biomarkers of disease risk, diagnosis, and prognosis. To advance the field of metabolomics, the National Institutes of Health (NIH) is investing

EFFECT OF INTERMITTENT DOSING REGIMENS OF ERLOTINIB ON METHYLNITROSOUREA-INDUCED MAMMARY CARCINOGENESIS

65 million through the NIH Common Fund’s Metabolomics Program, which will support comprehensive metabolomics resource cores, training in metabolomics, metabolomics technology development, metabolomics reference standards synthesis, and data sharing and international collaboration. While this infrastructure will be essential, there remain several challenges to broad implementation of metabolomics in population-based studies. To facilitate the use of metabolomics in population-based studies, the NIH-sponsored ‘Think Tank on the Use of Metabolomics in Population-Based Research’ was held to discuss the current opportunities and challenges of the field and identify potential solutions and/or strategies to address challenges. Insights and conclusions gained from the Think Tank are summarized here.

Accumulating Data to Optimally Predict Obesity Treatment (ADOPT) Core Measures: Behavioral Domain

EGF receptor (EGFR) inhibitors are used in the therapy of lung and pancreatic cancers and effectively prevent cancers in multiple animal models. Although daily dosing with erlotinib is effective, weekly dosing may reduce toxicity and have advantages, particularly for prevention. We tested alternative dosing regimens for preventive/therapeutic efficacy in a rat mammary cancer model. For prevention, erlotinib was administered by gavage beginning 5 days after methylnitrosourea (MNU). For therapy and biomarker studies, rats with palpable mammary cancers were treated for six weeks or for six days, respectively. Experiment A, erlotinib (6 mg/kg body weight/day, intragastric): daily (7 times/week); one day on/one day off; and two days on/two days off. All regimens decreased tumor incidence, increased tumor latency, and decreased cancer multiplicity versus controls (P < 0.01). However, intermittent dosing was less effective than daily dosing (P < 0.05). Experiment B, erlotinib (6 mg/kg body weight/day) daily or two days on/two days off or one time per week at 42 mg/kg body weight. All regimens reduced cancer incidence and multiplicity versus controls (P < 0.01). Interestingly, daily and weekly dosing were equally effective (P > 0.5). Experiment C, erlotinib administered at 42 or 21 mg/kg body weight 1 time per week, decreased tumor incidence and multiplicity (P < 0.01). Erlotinib had a serum half-life of ≤8 hours and weekly treatment yielded effective serum levels for ≤48 hours. Daily or weekly treatment of cancer bearing rats reduced mammary tumor size 25% to 35%, whereas control cancers increased >250%. Levels of phosphorylated extracellular signal-regulated kinase (ERK) were strongly decreased in rats treated daily/weekly with erlotinib. Thus, altering the dose of erlotinib retained most of its preventive and therapeutic efficacy, and based on prior clinical studies, is likely to reduce its toxicity. Cancer Prev Res; 6(5); 448–54. ©2013 AACR.