The Use of Three-Dimensional Images and Food Descriptions from a Smartphone Device Is Feasible and Accurate for Dietary Assessment.

Technology-assisted dietary assessment has the potential to improve the accuracy of self-reported dietary intake. This study evaluates MealScan3D (MS3D), a mobile device-based food recording system, which uses three-dimensional images to obtain food volumes and an application to capture algorithm-driven food intake data. Participants (n = 179) were randomly assigned and trained to record three meals using either MS3D or a written food record (WFR). Generous amounts of standardized meals were provided, and participants self-selected portions for each food. The weights of provided and uneaten/leftover foods were used to determine true intake. For total energy intake (three meals combined), validity (Pearson correlation) was significantly higher for MS3D vs. the WFR (p < 0.001); when interpreted as the percentage of variance in energy intake explained, MS3D explained 84.6% of true variance, a 25.3% absolute and 42.6% relative increase over the 59.3% explained by the WFR. For 9 of 15 individual foods, the Pearson correlations between true and reported portion size estimates were significantly larger for MS3D than the WFR. Bias was smaller (intercepts were closer to the means) for 9 of 15 foods and the regression coefficients for 10 of 15 foods were significantly closer to 1.0 in the MS3D arm. MS3D is feasible for dietary assessment and may provide improvements in accuracy compared to WFRs.

Change in plasma α-tocopherol associations with attenuated pulmonary function decline and with CYP4F2 missense variation.

BACKGROUND: Vitamin E (vitE) is hypothesized to attenuate age-related decline in pulmonary function. OBJECTIVES: We investigated the association between change in plasma vitE (∆vitE) and pulmonary function decline [forced expiratory volume in the first second (FEV1)] and examined genetic and nongenetic factors associated with ∆vitE. METHODS: We studied 1144 men randomly assigned to vitE in SELECT (Selenium and Vitamin E Cancer Prevention Trial). ∆vitE was the difference between baseline and year 3 vitE concentrations measured with GC-MS. FEV1 was measured longitudinally by spirometry. We genotyped 555 men (vitE-only arm) using the Illumina Expanded Multi-Ethnic Genotyping Array (MEGAex). We used mixed-effects linear regression modeling to examine the ∆vitE-FEV1 association. RESULTS: Higher ∆vitE was associated with lower baseline α-tocopherol (α-TOH), higher baseline γ-tocopherol, higher baseline free cholesterol, European ancestry (as opposed to African) (all P < 0.05), and the minor allele of a missense variant in cytochrome P450 family 4 subfamily F member 2 (CYP4F2) (rs2108622-T; 2.4 µmol/L higher ∆vitE, SE: 0.8 µmol/L; P = 0.0032). Higher ∆vitE was associated with attenuated FEV1 decline, with stronger effects in adherent participants (≥80% of supplements consumed): a statistically significant ∆vitE × time interaction (P = 0.014) indicated that a 1-unit increase in ∆vitE was associated with a 2.2-mL/y attenuation in FEV1 decline (SE: 0.9 mL/y). The effect size for 1 SD higher ∆vitE (+4 µmol/mmol free-cholesterol-adjusted α-TOH) was roughly one-quarter of the effect of 1 y of aging, but in the opposite direction. The ∆vitE-FEV1 association was similar in never smokers (2.4-mL/y attenuated FEV1 decline, SE: 1.0 mL/y; P = 0.017, n = 364), and current smokers (2.8-mL/y, SE: 1.6 mL/y; P = 0.079, n = 214), but there was little to no effect in former smokers (-0.64-mL/y, SE: 0.9 mL/y; P = 0.45, n = 564). CONCLUSIONS: Greater response to vitE supplementation was associated with attenuated FEV1 decline. The response to supplementation differed by rs2108622 such that individuals with the C allele, compared with the T allele, may need a higher dietary intake to reach the same plasma vitE concentration.

A Novel Mobile Structured Light System in Food 3D Reconstruction and Volume Estimation.

. Over the past ten years, diabetes has rapidly become more prevalent in all age demographics and especially in children. Improved dietary assessment techniques are necessary for epidemiological studies that investigate the relationship between diet and disease. Current nutritional research is hindered by the low accuracy of traditional dietary intake estimation methods used for portion size assessment. This paper presents the development and validation of a novel instrumentation system for measuring accurate dietary intake for diabetic patients. This instrument uses a mobile Structured Light System (SLS), which measures the food volume and portion size of a patient's diet in daily living conditions. The SLS allows for the accurate determination of the volume and portion size of a scanned food item. Once the volume of a food item is calculated, the nutritional content of the item can be estimated using existing nutritional databases. The system design includes a volume estimation algorithm and a hardware add-on that consists of a laser module and a diffraction lens. The experimental results demonstrate an improvement of around 40% in the accuracy of the volume or portion size measurement when compared to manual calculation. The limitations and shortcomings of the system are discussed in this manuscript.

Peripheral Zone Inflammation Is Not Strongly Associated With Lower Urinary Tract Symptom Incidence and Progression in the Placebo Arm of the Prostate Cancer Prevention Trial .

BACKGROUND: Intraprostatic inflammation has been associated with lower urinary tract symptom (LUTS) progression. However, prior studies used tissue removed for clinical indications, potentially skewing inflammation extent or biasing the association. We, therefore, evaluated inflammation and LUTS incidence and progression in men who underwent biopsy of the prostate peripheral zone irrespective of indication. MATERIALS AND METHODS: We developed nested case-control sets in men in the placebo arm of the Prostate Cancer Prevention Trial who were free of clinical BPH and had a protocol-directed year 7 biopsy. Cases had baseline IPSS <15 and year 7 IPSS of 8-14 (low, N = 47), 15-19 (incident moderate, N = 42), or ≥20 (incident high, N = 44). Controls had baseline and year 7 IPSS <8 (N = 41). For progression from IPSS <8, cases had baseline to year 7 IPSS slope >75th percentile (N = 46) and controls had a slope <25th percentile (N = 45). For progression from IPSS = 8-14, cases had a slope >75th percentile (N = 46) and controls had a slope <25th percentile (N = 46). We reviewed three H&E-stained biopsy cores per man to determine prevalence of ≥1 core with inflammation and mean extent (%) of tissue area with inflammation. RESULTS: Inflammation prevalence in low cases (64%) was similar to controls (66%), but higher in moderate (69%) and high (73%) cases (P-trend = 0.4). Extent did not differ across LUTS categories (P-trend = 0.5). For progression from IPSS < 8, prevalence (65%, P = 0.9) and extent (2.5%, P = 0.8) in cases did not differ from controls (64%, 2.7%). For progression from IPSS 8-14, prevalence in cases (52%) was lower than in controls (78%, P = 0.009), while extent was higher in cases (5.3%) than controls (3.6%), especially in men with ≥1 core with inflammation (10.1% versus 4.6%, P = 0.06). CONCLUSION: Peripheral zone intraprostatic inflammation is not strongly associated with LUTS incidence or progression. Prostate 76:1399-1408, 2016. © 2016 Wiley Periodicals, Inc.

Inflammation in Benign Prostate Tissue and Prostate Cancer in the Finasteride Arm of the Prostate Cancer Prevention Trial.

BACKGROUND: A previous analysis of the placebo arm of the Prostate Cancer Prevention Trial (PCPT) reported 82% overall prevalence of intraprostatic inflammation and identified a link between inflammation and higher-grade prostate cancer and serum PSA. Here, we studied these associations in the PCPT finasteride arm. METHODS: Prostate cancer cases (N = 197) detected either on a clinically indicated biopsy or on protocol-directed end-of-study biopsy, and frequency-matched controls (N = 248) with no cancer on an end-of-study biopsy were sampled from the finasteride arm. Inflammation in benign prostate tissue was visually assessed using digital images of hematoxylin and eosin-stained sections. Logistic regression was used for statistical analysis. RESULTS: In the finasteride arm, 91.6% of prostate cancer cases and 92.4% of controls had at least one biopsy core with inflammation in benign areas (P < 0.001 for difference compared with placebo arm). Overall, the odds of prostate cancer did not differ by prevalence [OR, 0.90; 95% confidence interval (CI), 0.44-1.84] or extent (P trend = 0.68) of inflammation. Inflammation was not associated with higher-grade disease (prevalence: OR, 1.07; 95% CI, 0.43-2.69). Furthermore, mean PSA concentration did not differ by the prevalence or extent of inflammation in either cases or controls. CONCLUSION: The prevalence of intraprostatic inflammation was higher in the finasteride than placebo arm of the PCPT, with no association with higher-grade prostate cancer. IMPACT: Finasteride may attenuate the association between inflammation and higher-grade prostate cancer. Moreover, the missing link between intraprostatic inflammation and PSA suggests that finasteride may reduce inflammation-associated PSA elevation.

Difference in Association of Obesity With Prostate Cancer Risk Between US African American and Non-Hispanic White Men in the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

IMPORTANCE: African American men have the highest rates of prostate cancer incidence and mortality in the United States. Understanding underlying reasons for this disparity could identify preventive interventions important to African American men. OBJECTIVE: To determine whether the association of obesity with prostate cancer risk differs between African American and non-Hispanic white men and whether obesity modifies the excess risk associated with African American race. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 3398 African American and 22,673 non-Hispanic white men who participated in the Selenium and Vitamin E Cancer Prevention Trial (2001-2011) with present analyses completed in 2014. MAIN OUTCOMES AND MEASURES: Total, low-grade (Gleason score <7), and high-grade (Gleason score ≥7) prostate cancer incidence. RESULTS: With a median (interquartile range) follow-up of 5.6 (1.8) years, there were 270, 148, and 88 cases of total, low-, and high-grade prostate cancers among African American men and a corresponding 1453, 898, and 441 cases in non-Hispanic white men, respectively. Although not associated with risk among non-Hispanic white men, BMI was positively associated with an increase in risk among African American men (BMI, <25 vs ≥35: hazard ratio [HR], 1.49 [95% CI, 0.95, 2.34]; P for trend = .03). Consequently, the risk associated with African American race increased from 28% (HR, 1.28 [95% CI, 0.91-1.80]) among men with BMI less than 25 to 103% (HR, 2.03 [95% CI, 1.38-2.98]) among African American men with BMI at least 35 (P for trend = .03). Body mass index was inversely associated with low-grade prostate cancer risk within non-Hispanic white men (BMI, <25 vs ≥35: HR, 0.80 [95% CI, 0.58-1.09]; P for trend = .02) but positively associated with risk within African American men (BMI, <25 vs ≥35: HR, 2.22 [95% CI, 1.17-4.21]; P for trend = .05). Body mass index was positively associated with risk of high-grade prostate cancer in both non-Hispanic white men (BMI, <25 vs ≥35: HR, 1.33 [95% CI, 0.90-1.97]; P for trend = .01) and African American men, although the increase may be larger within African American men, albeit the racial interaction was not statistically significant (BMI, <25 vs ≥35: HR, 1.81 [95% CI, 0.79-4.11]; P for trend = .02). CONCLUSIONS AND RELEVANCE: Obesity is more strongly associated with increased prostate cancer risk among African American than non-Hispanic white men and reducing obesity among African American men could reduce the racial disparity in cancer incidence. Additional research is needed to elucidate the mechanisms underlying the differential effects of obesity in African American and non-Hispanic white men.

Association between Serum Phospholipid Fatty Acids and Intraprostatic Inflammation in the Placebo Arm of the Prostate Cancer Prevention Trial.

Inflammation may play an etiologic role in prostate cancer. Several dietary factors influence inflammation; studies have shown that long-chain n-3 polyunsaturated fatty acids are anti-inflammatory, whereas n-6 and trans fatty acids are proinflammatory. We evaluated whether serum phospholipid n-3, n-6, and trans fatty acids were associated with intraprostatic inflammation, separately in 191 prostate cancer cases and 247 controls from the placebo arm of the Prostate Cancer Prevention Trial (PCPT). Men without a prostate cancer diagnosis underwent prostate biopsy at trial end, and benign prostate tissue inflammation was evaluated in approximately three biopsy cores per man; this was expressed as no, some, or all cores with inflammation. In controls, serum eicosapentaenoic acid [OR of all cores with inflammation versus none (95% CI), 0.35 (0.14-0.89)] and docosahexaenoic acid [OR (95% CI), 0.42 (0.17-1.02)] were inversely associated with, whereas linoleic acid [OR (95% CI), 3.85 (1.41-10.55)] was positively associated with intraprostatic inflammation. Serum trans fatty acids were not associated with intraprostatic inflammation. No significant associations were observed in cases; however, we could not rule out a positive association with linoleic acid and an inverse association with arachidonic acid. Thus, in the PCPT, we found that serum n-3 fatty acids were inversely, n-6 fatty acids were positively, and trans fatty acids were not associated with intraprostatic inflammation in controls. Although, in theory, inflammation could mediate associations of serum fatty acids with prostate cancer risk, our findings cannot explain the epidemiologic associations observed with n-3 and n-6 fatty acids.

A randomized controlled trial of vitamin E and selenium on rate of decline in lung function.

BACKGROUND: The intake of nutrients with antioxidant properties is hypothesized to augment antioxidant defenses, decrease oxidant damage to tissues, and attenuate age-related rate of decline in lung function. The objective was to determine whether long-term intervention with selenium and/or vitamin E supplements attenuates the annual rate of decline in lung function, particularly in cigarette smokers. METHODS: The Respiratory Ancillary Study (RAS) tested the single and joint effects of selenium (200 µg/d L-selenomethionine) and vitamin E (400 IU/day all rac-α-tocopheryl acetate) in a randomized double-blind placebo-controlled trial. At the end of the intervention, 1,641 men had repeated pulmonary function tests separated by an average of 3 years. Linear mixed-effects regression models estimated the effect of intervention on annual rate of decline in lung function. RESULTS: Compared to placebo, intervention had no main effect on either forced expiratory volume in the first second (FEV1) or forced expiratory flow (FEF25-75). There was no evidence for a smoking by treatment interaction for FEV1, but selenium attenuated rate of decline in FEF25-75 in current smokers (P = 0.0219). For current smokers randomized to selenium, annual rate of decline in FEF25-75 was similar to the annual decline experienced by never smokers randomized to placebo, with consistent effects for selenium alone and combined with vitamin E. CONCLUSIONS: Among all men, there was no effect of selenium and/or vitamin E supplementation on rate of lung function decline. However, current smokers randomized to selenium had an attenuated rate of decline in FEF25-75, a marker of airflow. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00241865 .

Effect of finasteride on serum androstenedione and risk of prostate cancer within the prostate cancer prevention trial: differential effect on high- and low-grade disease.

OBJECTIVE: To evaluate the effect of finasteride on serum androst-4-ene-3,17-dione (androstenedione) and its association with prostate cancer risk among subjects who participated in the Prostate Cancer Prevention Trial. METHODS: We analyzed serum androstenedione levels in 317 prostate cancer cases and 353 controls, nested in the Prostate Cancer Prevention Trial, a randomized placebo-controlled trial that found finasteride decreased prostate cancer risk. Androstenedione is the second most important circulating androgen in men besides testosterone and also a substrate for 5α-reductase enzyme. RESULTS: We observed a 22% increase in androstenedione levels compared with the baseline values in subjects who were treated with finasteride for 3 years. This significant increase did not vary by case-control status. Adjusted odds ratio and 95% confidence interval for the third tertile of absolute change in androstenedione levels compared with the first tertile were 0.42 (95% confidence interval, 0.19-0.94) for low-grade (Gleason score <7) cases. Similar results were observed when analyzed using percent change. There were no significant associations between serum androstenedione levels and the risk of high-grade disease. CONCLUSION: The results of this nested case-control study confirm that finasteride blocks the conversion of testosterone to dihydrotestosterone (DHT) and of androstenedione to 5α-androstanedione-3,17-dione, which also leads to the reduction of DHT formation. This decrease in DHT may help reduce the risk of low-grade prostate cancer in men. Our data on a differential effect of androstenedione also suggest that some high-grade prostate cancers may not require androgen for progression.

Circulating fatty acids and prostate cancer risk: individual participant meta-analysis of prospective studies.

BACKGROUND: Individual studies have suggested that some circulating fatty acids are associated with prostate cancer risk, but have not been large enough to provide precise estimates of associations, particularly by stage and grade of disease. METHODS: Principal investigators of prospective studies on circulating fatty acids and prostate cancer were invited to collaborate. Investigators provided individual participant data on circulating fatty acids (weight percent) and other characteristics of prostate cancer cases and controls. Prostate cancer risk by study-specific fifths of 14 fatty acids was estimated using multivariable-adjusted conditional logistic regression. All statistical tests were two-sided. RESULTS: Five thousand and ninety-eight case patients and 6649 control patients from seven studies with an average follow-up of 5.1 (SD = 3.3) years were included. Stearic acid (18:0) was inversely associated with total prostate cancer (odds ratio [OR] Q5 vs Q1 = 0.88, 95% confidence interval [CI] = 0.78 to 1.00, P trend = .043). Prostate cancer risk was, respectively, 14% and 16% greater in the highest fifth of eicosapentaenoic acid (20:5n-3) (OR = 1.14, 95% CI = 1.01 to 1.29, Ptrend = .001) and docosapentaenoic acid (22:5n-3) (OR = 1.16, 95% CI = 1.02 to 1.33, P trend = .003), but in each case there was heterogeneity between studies (P = .022 and P < .001, respectively). There was heterogeneity in the association between docosapentaenoic acid and prostate cancer by grade of disease (P = .006); the association was statistically significant for low-grade disease but not high-grade disease. The remaining 11 fatty acids were not statistically associated with total prostate cancer risk. CONCLUSION: There was no strong evidence that circulating fatty acids are important predictors of prostate cancer risk. It is not clear whether the modest associations of stearic, eicosapentaenoic, and docosapentaenoic acid are causal.

Cruciferous vegetables have variable effects on biomarkers of systemic inflammation in a randomized controlled trial in healthy young adults.

BACKGROUND: Isothiocyanates in cruciferous vegetables modulate signaling pathways critical to carcinogenesis, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a central regulator of inflammation. Glutathione S-transferase (GST) M1 and GSTT1 metabolize isothiocyanates; genetic variants may result in differences in biologic response. OBJECTIVE: The objective of this study was to test whether consumption of cruciferous or cruciferous plus apiaceous vegetables altered serum concentrations of interleukin (IL)-6, IL-8, C-reactive protein (CRP), tumor necrosis factor (TNF) α, and soluble TNF receptor (sTNFR) I and II, and whether this response was GSTM1/GSTT1 genotype dependent. METHODS: In a randomized crossover trial, healthy men (n = 32) and women (n = 31) aged 20-40 y consumed 4 14-d controlled diets: basal (vegetable-free), single-dose cruciferous (1xC) [7 g vegetables/kg body weight (BW)], double-dose cruciferous (2xC) (14 g/kg BW), and cruciferous plus apiaceous (carrot family) (1xC+A) vegetables (7 and 4 g/kg BW, respectively), with a 21-d washout period between each intervention. Urinary isothiocyanate excretion was also evaluated as a marker of systemic isothiocyanate exposure. Fasting morning blood and urine samples were collected on days 0 and 14 and analyzed. RESULTS: IL-6 concentrations were significantly lower on day 14 of the 2xC and 1xC+A diets than with the basal diet [-19% (95% CI: -30%, -0.1%) and -20% (95% CI: -31%, -0.7%), respectively]. IL-8 concentrations were higher after the 1xC+A diet (+16%; 95% CI: 4.2%, 35.2%) than after the basal diet. There were no effects of diet on CRP, TNF-α, or sTNFRI or II. There were significant differences between GSTM1-null/GSTT1+ individuals for several biomarkers in response to 1xC+A compared with basal diets (CRP: -37.8%; 95% CI: -58.0%, -7.4%; IL-6: -48.6%; 95% CI: -49.6%, -12.0%; IL-8: 16.3%; 95% CI: 6.7%, 57.7%) and with the 2xC diet compared with the basal diet (IL-8: -33.2%; 95% CI: -43.0%, -1.4%; sTNFRI: -7.5%; 95% CI: -12.7%, -2.3%). There were no significant reductions in biomarker concentrations in response to diet among GSTM1+/GSTT1+ or GSTM1-null/GSTT1-null individuals. Twenty-four-hour urinary isothiocyanate excretion was not associated with any of the inflammation markers overall; however, IL-6 was inversely associated with total isothiocyanate excretion in GSTM1-null/GSTT1-null individuals (ß = -0.12; 95% CI: -0.19, -0.05). CONCLUSIONS: In this young, healthy population, consumption of cruciferous and apiaceous vegetables reduced circulating IL-6; however, results for other biomarkers of inflammation were not consistent.

Serum 25-hydroxyvitamin D concentrations and risk of prostate cancer: results from the Prostate Cancer Prevention Trial.

BACKGROUND: Epidemiologic studies have reported inconsistent associations of vitamin D and prostate cancer risk; however, few have adequately controlled for detection bias related to prostate-specific antigen (PSA) screening, and the results of many studies may be affected by occult prostate cancers among controls. METHODS: Data for this nested case-control analysis (n = 1,695 cases/1,682 controls) are from the Prostate Cancer Prevention Trial. Baseline serum was analyzed for 25-hydroxyvitamin D [25(OH)D]. The presence or absence of cancer was subsequently determined by prostate biopsy. Polytomous logistic regression models were used to estimate associations of 25(OH)D with risk of total, Gleason 2-6, Gleason 7, and Gleason 8-10 prostate cancer. Results are presented for placebo and finasteride arms separately and combined. RESULTS: There were no associations of serum 25(OH)D with total prostate cancer risk. For Gleason 2-6 cancers, results were inconsistent across treatment arms with a suggestion of increased risk in the placebo arm only; however, there was no dose-response relationship. For Gleason 8-10 prostate cancers, 25(OH)D concentrations were associated with a linear decrease in risk among combined treatment arms [quartile 4 vs. 1: OR, 0.55; 95% confidence interval (CI), 0.32-0.94; P(trend) = 0.04]. These findings were somewhat stronger among men ≥65 versus 55-64 years at baseline (quartile 4 vs. 1: OR, 0.40; 95% CI, 0.18-0.88 vs. OR, 0.73; 95% CI, 0.35-1.52, respectively; P(interaction) = 0.52). CONCLUSIONS: Higher serum 25(OH)D may modestly increase risk of Gleason 2-6 disease and more substantially reduce risk of Gleason 8-10 prostate cancer. IMPACT: Vitamin D may have different effects for different stages of prostate cancers.

Chronic inflammation in benign prostate tissue is associated with high-grade prostate cancer in the placebo arm of the prostate cancer prevention trial.

BACKGROUND: Chronic inflammation is hypothesized to influence prostate cancer development, although a definitive link has not been established. METHODS: Prostate cancer cases (N = 191) detected on a for-cause (clinically indicated) or end-of-study (protocol directed) biopsy, and frequency-matched controls (N = 209), defined as negative for cancer on an end-of-study biopsy, were sampled from the placebo arm of the Prostate Cancer Prevention Trial. Inflammation prevalence and extent in benign areas of biopsy cores were visually assessed using digital images of hematoxylin and eosin-stained sections. Logistic regression was used to estimate associations. RESULTS: Of note, 86.2% of cases and 78.2% of controls had at least one biopsy core (of three assessed) with inflammation in benign areas, most of which was chronic. Men who had at least one biopsy core with inflammation had 1.78 [95% confidence interval (CI), 1.04-3.06] times the odds of prostate cancer compared with men who had zero cores with inflammation. The association was stronger for high-grade disease (Gleason sum 7-10, N = 94; OR, 2.24; 95% CI, 1.06-4.71). These patterns were present when restricting to cases and controls in whom intraprostatic inflammation was the least likely to have influenced biopsy recommendation because their prostate-specific antigen (PSA) was low (<2 ng/mL at biopsy). CONCLUSION: Inflammation, most of which was chronic, was common in benign prostate tissue, and was positively associated with prostate cancer, especially high grade. The association did not seem to be due to detection bias. IMPACT: This study supports an etiologic link between inflammation and prostate carcinogenesis, and suggests an avenue for prevention by mitigating intraprostatic inflammation.

Plasma vitamin D and prostate cancer risk: results from the Selenium and Vitamin E Cancer Prevention Trial.

BACKGROUND: In vitro, animal, and ecological studies suggest that inadequate vitamin D intake could increase prostate cancer risk, but results of biomarker-based longitudinal studies are inconsistent. METHODS: Data for this case (n = 1,731) and cohort (n = 3,203) analysis are from the Selenium and Vitamin E Cancer Prevention Trial. Cox proportional hazard models were used to test whether baseline plasma vitamin D (25-hydroxy) concentration, adjusted for season of blood collection, was associated with the risk of total and Gleason score 2-6, 7-10, and 8-10 prostate cancer. RESULTS: There were U-shaped associations of vitamin D with total cancer risk: compared with the first quintile, HRs were 0.83 [95% confidence interval (CI), 0.66-1.03; P = 0.092], 0.74 (95% CI, 0.59-0.92; P = 0.008), 0.86 (95% CI, 0.69-1.07; P = 0.181), and 0.98 (95% CI, 0.78-1.21; P = 0.823), for the second through fifth quintiles, respectively. For Gleason 7-10 cancer, corresponding HRs were 0.63 (95% CI, 0.45-0.90; P = 0.010), 0.66 (95% CI, 0.47-0.92; P = 0.016), 0.79 (95% CI, 0.56-1.10; P = 0.165), and 0.88 (95% CI, 0.63-1.22; P = 0.436). Among African American men (n = 250 cases), higher vitamin D was associated with reduced risk of Gleason 7-10 cancer only: in the a posteriori contrast of quintiles 1-2 versus 3-5, the HR was 0.55 (95% CI, 0.31-0.97; P = 0.037), with no evidence of dose-response or a U-shaped association. CONCLUSIONS: Both low and high vitamin D concentrations were associated with increased risk of prostate cancer, and more strongly for high-grade disease. IMPACT: The optimal range of circulating vitamin D for prostate cancer prevention may be narrow. Supplementation of men with adequate levels may be harmful. Cancer Epidemiol Biomarkers Prev; 23(8); 1494-504. ©2014 AACR.

A stable isotope biomarker of marine food intake captures associations between n-3 fatty acid intake and chronic disease risk in a Yup'ik study population, and detects new associations with blood pressure and adiponectin.

The nitrogen isotope ratio (δ(15)N) of RBCs has been proposed as a biomarker of marine food intake in Yup'ik people based on strong associations with RBC eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). However, EPA and DHA derive from marine fats, whereas elevated δ(15)N derives from marine protein, and these dietary components may have different biologic effects. Whether δ(15)N is similarly associated with chronic disease risk factors compared with RBC EPA and DHA is not known. We used covariate-adjusted linear models to describe biomarker associations with chronic disease risk factors in Yup'ik people, first in a smaller (n = 363) cross-sectional study population using RBC EPA, DHA, and δ(15)N, and then in a larger (n = 772) cross-sectional study population using δ(15)N only. In the smaller sample, associations of RBC EPA, DHA, and δ(15)N with obesity and chronic disease risk factors were similar in direction and significance: δ(15)N was positively associated with total, HDL, and LDL cholesterol, apolipoprotein A-I, and insulin-like growth factor binding protein-3 (IGFBP-3), and inversely associated with triglycerides. Based on comparisons between covariate-adjusted ß-coefficients, EPA was more strongly associated with circulating lipids and lipoproteins, whereas δ(15)N was more strongly associated with adipokines, the inflammatory marker interleukin-6, and IGFBP-3. In the larger sample there were new findings for this population: δ(15)N was inversely associated with blood pressure and there was a significant association (with inverse linear and positive quadratic terms) with adiponectin. In conclusion, δ(15)N is a valid measure for evaluating associations between EPA and DHA intake and chronic disease risk in Yup'ik people and may be used in larger studies. By measuring δ(15)N, we report beneficial associations of marine food intake with blood pressure and adiponectin, which may contribute to a lower incidence of some chronic diseases in Yup'ik people.

Baseline selenium status and effects of selenium and vitamin e supplementation on prostate cancer risk.

BACKGROUND: The Selenium and Vitamin E Cancer Prevention Trial found no effect of selenium supplementation on prostate cancer (PCa) risk but a 17% increased risk from vitamin E supplementation. This case-cohort study investigates effects of selenium and vitamin E supplementation conditional upon baseline selenium status. METHODS: There were 1739 total and 489 high-grade (Gleason 7-10) PCa cases and 3117 men in the randomly selected cohort. Proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for effects of supplementation within quintiles of baseline toenail selenium. Cox proportional hazards models were used to estimate hazard ratios, and all statistical tests are two-sided. RESULTS: Toenail selenium, in the absence of supplementation, was not associated with PCa risk. Selenium supplementation (combined selenium only and selenium + vitamin E arms) had no effect among men with low selenium status (<60th percentile of toenail selenium) but increased the risk of high-grade PCa among men with higher selenium status by 91% (P = .007). Vitamin E supplementation (alone) had no effect among men with high selenium status (≥40th percentile of toenail selenium) but increased the risks of total, low-grade, and high-grade PCa among men with lower selenium status (63%, P = .02; 46%, P = .09; 111%, P = .008, respectively). CONCLUSIONS: Selenium supplementation did not benefit men with low selenium status but increased the risk of high-grade PCa among men with high selenium status. Vitamin E increased the risk of PCa among men with low selenium status. Men should avoid selenium or vitamin E supplementation at doses that exceed recommended dietary intakes.

Statin drug use is not associated with prostate cancer risk in men who are regularly screened.

PURPOSE: Prospective cohort studies support the hypothesis that statin drug users have a lower risk of aggressive prostate cancer. Whether statin drug use influences the risk of screen detected disease is less clear, possibly because of complex detection biases. Thus, we investigated this association in a setting in which men had low baseline serum prostate specific antigen concentration and were screened annually. MATERIALS AND METHODS: We performed a cohort study of 9,457 men 55 years old or older at randomization to the placebo arm of PCPT (Prostate Cancer Prevention Trial). The men reported new use of medications quarterly. We estimated the multivariable adjusted HR of prostate cancer (574 cases in 62,192 person-years) for statin drug use and duration of use during the trial using Cox proportional hazards regression. RESULTS: During 7 years of followup statin drug use during the trial was not associated with the risk of total prostate cancer (HR 1.03, 95% CI 0.82-1.30), or lower grade (HR 0.96, 95% CI 0.71-1.29) or higher grade (HR 1.27, 95% CI 0.85-1.90) prostate cancer. Duration of use during followup was also not associated with the risk of total, or lower or higher grade disease (p trend=0.7, 0.5 and 0.2, respectively). CONCLUSIONS: These prospective results do not support the hypothesis that statin drugs protect against prostate cancer in the setting of regular prostate cancer screening.

Intake of long-chain ω-3 fatty acids from diet and supplements in relation to mortality.

Evidence from experimental studies suggests that the long-chain ω-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid have beneficial effects that may lead to reduced mortality from chronic diseases, but epidemiologic evidence is mixed. Our objective was to evaluate whether intake of long-chain ω-3 fatty acids from diet and supplements is associated with cause-specific and total mortality. Study participants (n = 70,495) were members of a cohort study (the Vitamins and Lifestyle Study) who were residents of Washington State aged 50-76 years at the start of the study (2000-2002). Participants were followed for mortality through 2006 (n = 3,051 deaths). Higher combined intake of eicosapentaenoic acid and docosahexaenoic acid from diet and supplements was associated with a decreased risk of total mortality (hazard ratio (HR) = 0.82, 95% confidence interval (CI): 0.73, 0.93) and mortality from cancer (HR = 0.77, 95% CI: 0.64, 0.92) but only a small reduction in risk of death from cardiovascular disease (HR = 0.87, 95% CI: 0.68, 1.10). These results suggest that intake of long-chain ω-3 fatty acids may reduce risk of total and cancer-specific mortality.