Paige E. Farris

Folate Intake and Prostate Cancer Risk: A Case-Control Study

Folate deficiency has been implicated in the carcinogenesis of several tumor types. The role of folate in prostate cancer remains indeterminate. We investigated folate as a risk factor for prostate cancer among 140 biopsy-confirmed prostate cancer patients, 230 age-matched clinic controls, and 250 negative prostate biopsy controls. Dietary folate intake was inversely associated with overall risk of prostate cancer as compared to clinic controls (P for a linear trend = 0.003). When stratified by disease severity, dietary folate and folate from natural sources were associated with reduced risk of high-grade cancer as compared to both clinic controls (P for a linear trend = 0.0009 and 0.02, respectively) and biopsy negative controls (P for a linear trend = 0.03 and 0.05, respectively). There was no interaction between alcohol consumption and folate intake. These analyses support an inverse association between dietary folate intake and prostate cancer risk and primarily risk of high-grade prostate cancer.

Agent Orange as a risk factor for high-grade prostate cancer

Agent Orange (AO) exposure (AOe) is a potential risk factor for the development of prostate cancer (PCa). However, it is unknown whether AOe specifically increases the risk of lethal PCa. The objective of this study was to determine the association between AOe and the risk of detecting high‐grade PCa (HGPCa) (Gleason score ≥7) on biopsy in a US Veteran cohort.

Sulforaphane bioavailability and chemopreventive activity in women scheduled for breast biopsy

Epidemiologic studies suggest a protective effect of cruciferous vegetables on breast cancer. Sulforaphane (SFN), an active food component derived from crucifers, has been shown to be effective in breast cancer chemoprevention. This study evaluated the chemopreventive effect of SFN on selective biomarkers from blood and breast tissues. In a 2- to 8-week double-blinded, randomized controlled trial, 54 women with abnormal mammograms and scheduled for breast biopsy were randomized to consume a placebo or a glucoraphanin (GFN) supplement providing SFN (n = 27). Plasma and urinary SFN metabolites, peripheral blood mononuclear cell (PBMC) histone deacetylase (HDAC) activity, and tissue biomarkers (H3K18ac, H3K9ac, HDAC3, HDAC6, Ki-67, p21) were measured before and after the intervention in benign, ductal carcinoma in situ, or invasive ductal carcinoma breast tissues. Within the supplement group, Ki-67 (P = 0.003) and HDAC3 (P = 0.044) levels significantly decreased in benign tissue. Pre-to-postintervention changes in these biomarkers were not significantly different between treatment groups after multiple comparison adjustment. GFN supplementation was associated with a significant decrease in PBMC HDAC activity (P = 0.04). No significant associations were observed between SFN and examined tissue biomarkers when comparing treatment groups. This study provides evidence that GFN supplementation for a few weeks is safe but may not be sufficient for producing changes in breast tissue tumor biomarkers. Future studies employing larger sample sizes should evaluate alternative dosing and duration regimens to inform dietary SFN strategies in breast cancer chemoprevention. Cancer Prev Res; 8(12); 1184–91. ©2015 AACR.

Associations between cruciferous vegetable intake and selected biomarkers among women scheduled for breast biopsies

OBJECTIVE To examine the relationship between dietary cruciferous vegetable intake and selected tumour biomarkers for histone acetylation (H3K9ac, H3K18ac, HDAC3 and HDAC6), proliferation (Ki-67) and cell-cycle regulation (p21) from breast tissue. DESIGN The study used baseline data of women recruited to participate in a clinical trial of sulforaphane supplement. Dietary cruciferous vegetable intake was collected through a validated Arizona Cruciferous Vegetable Intake Questionnaire. Breast tissue was obtained from biopsy samples. Spearman correlations were calculated between intake of specific cruciferous vegetables and biomarkers. Tissue biomarkers were log2-transformed to obtain approximate normality. Linear regression analyses were conducted to examine associations between cruciferous vegetable intake and biomarkers adjusting for age and use of non-steroidal anti-inflammatory drugs. False discovery rate (FDR) was used to account for multiple comparisons. SETTING Clinical trial baseline. SUBJECTS Fifty-four women who had abnormal mammogram findings and were scheduled for breast biopsy. RESULTS Mean intake of total cruciferous vegetables from all food sources was 81·7 (sd 57·3) g/d. Mean urinary total sulforaphane metabolites was 0·08 (sd 0·07) µm/mm creatinine. Total cruciferous vegetable intake was inversely associated with Ki-67 protein expression in breast ductal carcinoma in situ (DCIS) tissue (β=-0·004; se=0·001; FDR q value=0·03), but not in benign or invasive ductal carcinoma (IDC) tissue. No association was found for other biomarkers measured (HDAC3, HDAC6, H3K9, H3K18 and p21) in all tissues examined (benign, DCIS and IDC). CONCLUSIONS The present study sought to provide additional evidence for the potential role of sulforaphane in histone acetylation and cell proliferation. Here, we report that total cruciferous vegetable intake is associated with decreased cell proliferation in breast DCIS tissue.

Statins and Prostate Cancer Risk: A Case-Control Study

Observational studies have shown that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) use may be associated with reduced cancer risk. The purpose of this case-control study was to elucidate the association between statin use and prostate cancer risk. Prostate cancer cases (n = 100), recruited upon referral for prostate biopsy, and frequency age-matched, prostate-specific antigen-normal clinic controls (n = 202) were recruited from the Portland, Oregon, Veterans Affairs Medical Center. Information on any use of statins from May 1997 through August 2004 was obtained from an electronic pharmacy database. Days of use, type of statin, dose, and prescription changes were recorded. Duration and intensity were calculated for each statin type on the basis of days of use and prescribed dose. Thirty-six percent of cases and 49 percent of controls had a record of any statin use. Following adjustment for other potential risk factors, statin use was associated with a significant reduction in prostate cancer risk (odds ratio = 0.38, 95% confidence interval: 0.21, 0.69). Furthermore, in analyses stratified by Gleason score, the inverse association with statin use was maintained only among men with Gleason scores of > or =7 (odds ratio = 0.24, 95% confidence interval: 0.11, 0.53). The results of this case-control study suggest that statins may reduce the risk of total prostate cancer and, specifically, more aggressive prostate cancer.

Scaling Up and Tailoring the “Putting Public Health in Action” Training Curriculum

Despite access to a growing menu of evidence-based interventions, public health practitioners continue to underuse them, in part because practitioners may require new knowledge, skills, and resources to do so. Numerous foundations, universities, governmental agencies, and consultants are providing trainings to address the gaps in practitioners’ capacity. To most significantly affect population health, these trainings need to reach practitioners who may have limited access to on-site trainings. Despite the number of organizations offering trainings, little is known about how to scale up trainings to efficiently extend their reach or how to tailor trainings to the needs of different intervention. The Cancer Prevention and Control Research Network and its collaborating centers have developed a training curriculum and delivered it in both in-person and distance formats to a range of audiences. The purpose of this article is to describe the training curriculum and findings from the Network’s evaluation of approaches used to scale up delivery of the “Putting Public Health Evidence in Action” curriculum and tailor content for specific evidence-based interventions.

Effects of ω-3 Fatty Acids and Catechins on Fatty Acid Synthase in the Prostate: A Randomized Controlled Trial

ABSTRACT Animal and human studies suggest fish oil and green tea may have protective effect on prostate cancer. Fatty acid synthase (FAS) has been hypothesized to be linked to chemoprotective effects of both compounds. This study evaluated the independent and joint effects of fish oil (FO) and green tea supplement (epigallocatechin-3-gallate, EGCG) on FAS and Ki-67 levels in prostate tissue. Through a double-blinded, randomized controlled trial with 2 × 2 factorial design, 89 men scheduled for repeat prostate biopsy following an initial negative prostate biopsy were randomized into either FO alone (1.9 g DHA + EPA/day), EGCG alone (600 mg/day), a combination of FO and EGCG, or placebo. We used linear mixed-effects models to test the differences of prostate tissue FAS and Ki-67 by immunohistochemistry between pre- and post-intervention within each group, as well as between treatment groups. Results did not show significant difference among treatment groups in pre-to-post-intervention changes of FAS (P = 0.69) or Ki-67 (P = 0.26). Comparing placebo group with any of the treatment groups, we did not find significant difference in FAS or Ki-67 changes (all P > 0.05). Results indicate FO or EGCG supplementation for a short duration may not be sufficient to produce biologically meaningful changes in FAS or Ki-67 levels in prostate tissue.

Environmental, Behavioral, and Cultural Factors That Influence Healthy Eating in Rural Women of Childbearing Age Findings From a PhotoVoice Study

Despite increasing recognition of the role nutrition plays in the health of current and future generations, many women struggle to eat healthy. We used the PhotoVoice method to engage 10 rural women in identifying perceived barriers and facilitators to healthy eating in their homes and community. They took 354 photographs, selected and wrote captions for 62 images, and explored influential factors through group conversation. Using field notes and participant-generated captions, the research team categorized images into factors at the individual, relational, community/organizational, and societal levels of a socioecological model. Barriers included limited time, exposure to marketing, and the high cost of food. Facilitators included preparing food in advance and support from non-partners; opportunities to hunt, forage, and garden were also facilitators, which may be amplified in this rural environment. Nutritional interventions for rural women of childbearing age should be multi-component and focus on removing barriers at multiple socioecological levels.

The safety of prostate biopsy procedures in the research setting: A 10-year multicenter experience.

87 Background: The safety of routine prostate biopsies has recently been called into question, citing increasing rates of complications compared to historical data. We examined our experience with prostate biopsies done as a component of multiple clinical research trials. METHODS The safety of routine prostate biopsies has recently been called into question, citing increasing rates of complications compared to historical data. We examined our experience with prostate biopsies done as a component of multiple clinical research trials. RESULTS 141 charts had adequate documentation. A mean of 12 +/- 4 cores were obtained during the procedures (8-26). Of these patients, 136 of the 141 had no adverse events during or after their biopsies. Of the five adverse events, there were three (2.2%) minor and two (1.4%) major complications. The minor complication group consisted of three patients with mild, but prolonged hematuria (12-14 days). Of the two major complications, one patient had hematospermia for 28 days and the second patient was diagnosed with prostatitis 18 days after biopsy and required multiple antibiotics. No patient required any further intentions or hospitalizations. There was no correlation between complication rate and study type (p=0.662) or treatment setting (p=0.411). Overall, 96.5% of patients undergoing prostate biopsies for research purposes had no adverse events or complications related to the procedure. CONCLUSIONS Research related prostate biopsy procedures can be performed in a diverse range of treatment settings and do not incur any increased risk versus clinical biopsies.

Agent orange as a risk factor for high-grade prostate cancer detected on initial prostate biopsy.

4667 Background: Exposure to Agent Orange (AO), a defoliate used during the Vietnam War, is a potential risk factor for the development of prostate cancer (PCa). However, it is unknown whether individuals exposed to AO are at risk of a more aggressive phenotype of PCa than individuals not exposed to AO. The goal of this study was to determine the association between AO exposure and risk of high-grade PCa in a cohort of veterans referred for an initial prostate biopsy. METHODS Risk factors were identified using historical clinical data from individuals referred to the Portland VA Hospital for a prostate biopsy between 1993 and 2010. Covariates evaluated include AO exposure, prostate-specific antigen density (PSAD), digital rectal exam (DRE), age, family history, body mass index (BMI), race, and service history. Outcomes of the biopsies were defined as high-grade PCa (HGPCa, Gleason ≥ 7) vs. other [low-grade PCa (LGPCa, Gleason ≤ 6) or no PCa]. Multivariate logistic regression was used to estimate the risk of HGPCA in those with AO exposure. To determine whether AO exposure increased the risk of both HGPCa and LGPCa, separate multivariate models compared the odds of AO exposure in individuals with HGPCa or LGPCa vs. no PCa. RESULTS Of the 2720 veterans who underwent prostate biopsy, 896 (32.9%) were found to have PCa and 459 (16.9%) were found to have HGPCa. After adjustment for significant confounders including PSAD, DRE, and age, HGPCa cases were more likely to have been exposed to AO as compared to those with LGPCa or no PCa (aOR = 1.73, 95% CI: 1.14 to 2.62). In an analysis of HGPCa vs. no PCa, AO was strongly associated with HGPCa (aOR = 1.74, 95% CI: 1.12 to 2.73). In contrast, in an analysis of LGPCa vs. no cancer, AO exposure was not associated with the detection of LGPCa (aOR = 1.21, 95% CI: 0.80 to 1.85). Thus, AO exposure appeared to uniquely increase the risk of HGPCa in men presenting for an initial prostate biopsy. CONCLUSIONS Agent Orange exposure was associated with a significant increase in the risk of HGPCa in men referred for an initial prostate biopsy. If validated, these findings could aid in the development of effective PCa screening strategies for Vietnam-era veterans.