Genetic variants reflecting higher vitamin e status in men are associated with reduced risk of prostate cancer.

Abstract

Vitamin E (α-tocopherol) plays a key role in the regulation of cell growth and differentiation and has been studied as a potential chemopreventive agent for prostate cancer. The association of serum vitamin E concentrations with cancer risk may be modified by genetic variations in vitamin E-related genes. We examined whether variants in vitamin E-related genes were associated with risk of prostate cancer in a nested case-control study using 483 prostate cancer cases and 542 matched controls of European ancestry from a large U.S. multicenter trial that had available measurements of serum vitamin E concentrations and genotyping of 3 genome-wide association study meta-analysis-identified single-nucleotide polymorphisms (SNPs) associated with circulating vitamin E. ORs and 95% CIs were calculated using unconditional logistic regression adjusted for age, family history of prostate cancer, and serum total cholesterol. Findings suggest lower prostate cancer risk for men whose genotypes reflect higher vitamin E (i.e., α-tocopherol) status. An SNP (rs964184) near budding-site selection protein 13 (yeast) (BUD13), zinc finger protein 259 (ZNF259), and apolipoprotein A5 (APOA5) on 11q23.3 was significantly associated with prostate cancer risk (per-allele OR = 0.75; 95% CI: 0.58, 0.98; P-trend = 0.03). The association between rs964184 and prostate cancer risk was stronger among homozygous carriers of the minor allele (OR = 0.27; 95% CI: 0.09, 0.83). Another variant, rs11057830 in scavenger receptor class-B member 1 (SCARB1) on 12p24.31, approached statistical significance (OR = 0.32; 95% CI: 0.10, 1.01, P = 0.05; 2 minor allele copies). This study suggests that polymorphisms near BUD13/ZNF259/APOA5, involved in vitamin E transport and metabolism, may be associated with lower risk of prostate cancer. This trial was registered at clinicaltrials.gov as NCT00002540.

• Authors: Jacqueline M Major, Kai Yu, Stephanie J Weinstein, Sonja I Berndt, Paula L Hyland, Meredith Yeager, Stephen Chanock, Demetrius Albanes
• Journal: The Journal of nutrition (J Nutr) Vol. 144 Issue 5 Pg. 729-33 (May 2014) ISSN: 1541-6100 [Electronic] United States
• PMID: 24623848 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Intramural)

Chemical References

• APOA5 protein, human
• Apolipoprotein A-V
• Apolipoproteins A
• Carrier Proteins
• Membrane Transport Proteins
• SCARB1 protein, human
• Scavenger Receptors, Class B
• ZPR1 protein, human
• Vitamin E

Topics

• Aged
• Apolipoprotein A-V
• Apolipoproteins A (genetics)
• Carrier Proteins (genetics)
• Case-Control Studies
• Genetic Predisposition to Disease (epidemiology)
• Genetic Variation
• Genome-Wide Association Study
• Humans
• Male
• Mass Screening (methods)
• Membrane Transport Proteins
• Middle Aged
• Polymorphism, Single Nucleotide
• Prostatic Neoplasms (epidemiology, genetics, metabolism)
• Risk Factors
• Scavenger Receptors, Class B (genetics)
• United States (epidemiology)
• Vitamin E (blood, genetics)
• White People (genetics, statistics & numerical data)