Background: Observed associations between vitamin E status and certain cancers (e.g., lung, prostate, colorectal, cervical and ovarian) suggest a protective relation may exist, with many studies focusing on the antioxidant and antiproliferative properties of alpha-tocopherol. Recent findings suggest that gamma-tocopherol may play a similar role that is independent of alpha-tocopherol. The purpose of this study was to identify genetic variants associated with circulating levels of alpha- and gamma-tocopherol. This is the first genome-wide association study (GWAS) to examine these two nutritional phenotypes.

Methods: Prior to analysis, tocopherol levels were log-transformed to normalize the distributions. General linear models were used to relate the log-transformed outcomes to a SNP by assuming an additive mode of inheritance. Analyses were adjusted for the effects of age, cancer status, body mass index, and cholesterol (because it is well established that vitamin E levels are affected by circulating lipids).

Results: Based on the combined data from the two adult cohorts (the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study and the Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial (PLCO) cohorts) comprising 5,006 men of European descent, we found evidence of novel loci associated with circulating vitamin E, including BUD13 (rs964184, P=3.5 x 10-10), CYP4F2 (rs2108622, P=7.8 x 10-9), and SCARB1 (rs11057830, P=3.0 x 10-7), all of which meet genome-wide level of significance for their association with alpha-tocopherol. Our three identified single nucleotide polymorphisms (SNPs) have previously been reported to be associated with HDL cholesterol and triglycerides, which are involved in vitamin E transport. We further replicated the most significant findings in an independent data set of 2,769 women, with combined meta-analysis significance of P=1.1 x 10-12 (BUD13, rs964184), P=1.1 x 10-9 (CYP4F2, rs2108622), and P=3.5 x 10-8 (SCARB1, rs11057830). The genome-wide significant associations for gamma-tocopherol levels and SNPs in four gene regions did not replicate, however.

Conclusion: Our findings reveal specific, previously unknown proteins related to vitamin E biochemical status that add to our understanding of this membrane-integrated micronutrient and that can be investigated with respect to cancer and other disease phenotypes.

Citation Information: Cancer Prev Res 2010;3(12 Suppl):A88.

Copyright © 2010, American Association for Cancer Research
2010