Dataset Information

Plasma tocopherols and risk of prostate cancer in the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

ABSTRACT: The Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed higher prostate cancer incidence in men supplemented with high-dose ?-tocopherol. We, therefore, examined whether presupplementation plasma ?-tocopherol or ?-tocopherol was associated with overall or high-grade prostate cancer. A stratified case-cohort sample that included 1,746 incident prostate cancer cases diagnosed through June 2009 and a subcohort of 3,211 men was derived from the SELECT trial of 35,533 men. Plasma was collected at entry from 2001 to 2004, and median follow-up was 5.5 years (range, 0-7.9 years). Incidence of prostate cancer as a function of plasma ?-tocopherol, ?-tocopherol, and supplementation with ?-tocopherol or selenomethionine was estimated by the hazard ratio (HR). Plasma ?-tocopherol was not associated with prostate cancer. Men with higher ?-tocopherol concentrations seemed to have risk similar to that of men with lower concentrations [overall HR for fifth (Q5) vs. first quintile (Q1), 1.21; 95 % confidence interval (CI), 0.88-1.66; P-trend = 0.24; in the trial placebo arm, Q5 HR, 0.85; 95% CI, 0.44-1.62; P-trend = 0.66]. We found a strong positive plasma ?-tocopherol association among men receiving the trial selenomethionine supplement [Q5 HR, 2.04; 95% CI, 1.29-3.22; P-trend = 0.005]. A positive plasma ?-tocopherol-prostate cancer association also seemed limited to high-grade disease (Gleason grade, 7-10; overall Q5 HR, 1.59; 95% CI, 1.13-2.24; P-trend = 0.001; among men receiving selenomethionine, Q5 HR, 2.12; 95% CI, 1.32-3.40; P-trend = 0.0002). Our findings indicate that higher plasma ?-tocopherol concentrations may interact with selenomethionine supplements to increase high-grade prostate cancer risk, suggesting a biologic interaction between ?-tocopherol and selenium itself or selenomethionine.

SUBMITTER: Albanes D

PROVIDER: S-EPMC4408535 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Plasma tocopherols and risk of prostate cancer in the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

Albanes Demetrius D Till Cathee C Klein Eric A EA Goodman Phyllis J PJ Mondul Alison M AM Weinstein Stephanie J SJ Taylor Philip R PR Parnes Howard L HL Gaziano J Michael JM Song Xiaoling X Fleshner Neil E NE Brown Powel H PH Meyskens Frank L FL Thompson Ian M IM

Cancer prevention research (Philadelphia, Pa.) 20140624 9

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed higher prostate cancer incidence in men supplemented with high-dose α-tocopherol. We, therefore, examined whether presupplementation plasma α-tocopherol or γ-tocopherol was associated with overall or high-grade prostate cancer. A stratified case-cohort sample that included 1,746 incident prostate cancer cases diagnosed through June 2009 and a subcohort of 3,211 men was derived from the SELECT trial of 35,533 men. Plasma was colle ...[more]

PMID: 24961880

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Project description:The initial report of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) found no reduction in risk of prostate cancer with either selenium or vitamin E supplements but a statistically nonsignificant increase in prostate cancer risk with vitamin E. Longer follow-up and more prostate cancer events provide further insight into the relationship of vitamin E and prostate cancer.To determine the long-term effect of vitamin E and selenium on risk of prostate cancer in relatively healthy men.A total of 35,533 men from 427 study sites in the United States, Canada, and Puerto Rico were randomized between August 22, 2001, and June 24, 2004. Eligibility criteria included a prostate-specific antigen (PSA) of 4.0 ng/mL or less, a digital rectal examination not suspicious for prostate cancer, and age 50 years or older for black men and 55 years or older for all others. The primary analysis included 34,887 men who were randomly assigned to 1 of 4 treatment groups: 8752 to receive selenium; 8737, vitamin E; 8702, both agents, and 8696, placebo. Analysis reflect the final data collected by the study sites on their participants through July 5, 2011.Oral selenium (200 ?g/d from L-selenomethionine) with matched vitamin E placebo, vitamin E (400 IU/d of all rac-?-tocopheryl acetate) with matched selenium placebo, both agents, or both matched placebos for a planned follow-up of a minimum of 7 and maximum of 12 years.Prostate cancer incidence.This report includes 54,464 additional person-years of follow-up and 521 additional cases of prostate cancer since the primary report. Compared with the placebo (referent group) in which 529 men developed prostate cancer, 620 men in the vitamin E group developed prostate cancer (hazard ratio [HR], 1.17; 99% CI, 1.004-1.36, P = .008); as did 575 in the selenium group (HR, 1.09; 99% CI, 0.93-1.27; P = .18), and 555 in the selenium plus vitamin E group (HR, 1.05; 99% CI, 0.89-1.22, P = .46). Compared with placebo, the absolute increase in risk of prostate cancer per 1000 person-years was 1.6 for vitamin E, 0.8 for selenium, and 0.4 for the combination.Dietary supplementation with vitamin E significantly increased the risk of prostate cancer among healthy men.Clinicaltrials.gov Identifier: NCT00006392.

Project description: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.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.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.Total, low-grade (Gleason score <7), and high-grade (Gleason score ?7) prostate cancer incidence.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).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.

Project description:Vitamin D may influence prostate cancer risk, but evidence is inconsistent. We conducted a nested case-control study in the Prostate Cancer Prevention Trial (PCPT). Cases (n = 1,128) and controls (n = 1,205) were frequency matched on age, first-degree relative with prostate cancer, and PCPT treatment arm (finasteride/placebo); African-Americans were oversampled and case/control status was biopsy confirmed. We selected 21 SNPs in vitamin D-related genes (VDR, GC, C10orf88, CYP2R1, CYP24A1, CYP27B1, DHCR7, and NADSYN1) to test genotype and genotype-treatment interactions in relation to prostate cancer. We also tested mean serum 25(OH)D differences by minor allele distributions and tested for serum 25(OH)D-genotype interactions in relation to prostate cancer risk. Log-additive genetic models (Bonferroni-corrected within genes) adjusted for age, body mass index, PSA, and family history of prostate cancer revealed a significant interaction between treatment arm and GC/rs222016 (finasteride OR = 1.37, placebo OR = 0.85; P interaction < 0.05), GC/rs222014 (finasteride OR = 1.36, placebo OR = 0.85; P interaction < 0.05), and CYP27B1/rs703842 (finasteride OR = 0.76, placebo OR = 1.10; P interaction < 0.05) among Caucasians, and C10orf88/rs6599638 (finasteride OR = 4.68, placebo OR = 1.39; P interaction < 0.05) among African-Americans. VDR/rs1544410 and CYP27B1/rs703842 had significant treatment interactions for high-grade disease among Caucasians (finasteride OR = 0.81, placebo OR = 1.40; P interaction < 0.05 and finasteride OR = 0.70, placebo OR = 1.28; P interaction < 0.05, respectively). Vitamin D-related SNPs influenced serum 25(OH)D, but gene-serum 25(OH)D effect modification for prostate cancer was marginally observed only for CYP24A1/rs2248359. In conclusion, evidence that vitamin D-related genes or gene-serum 25(OH)D associations influence prostate cancer risk is modest. We found some evidence for gene-finasteride interaction effects for prostate cancer in Caucasians and African-Americans. Results suggest only minimal associations of vitamin D with total or high-grade prostate cancer.

Dataset Information

Plasma tocopherols and risk of prostate cancer in the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

Publications

Plasma tocopherols and risk of prostate cancer in the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

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