Background : Significant reductions in prostate cancer incidence and mortality were observed in men randomized to receive 50 mg supplemental vitamin E (α-tocopherol) daily in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. We hypothesized that variation in genes involved in vitamin E transport might directly affect prostate cancer risk and/or modify the observed effects of the vitamin E supplement. Methods : We investigated the associations between prostate cancer risk and nine single nucleotide polymorphisms (SNPs) in α-tocopherol transfer protein (TTPA) and tocopherol associated protein (TAP), which encode vitamin E-binding proteins involved in serum α-tocopherol accumulation and its delivery to various tissues, including the prostate, respectively. The study was conducted among 985 incident prostate cancer cases and 848 controls nested in the ATBC Study. Genotype-phenotype relations were also evaluated, as baseline and on-study serum α-tocopherol concentrations were available for all men. Results : We found little association between polymorphisms in either gene and overall prostate cancer risk. Findings were similar for advanced (stage III or IV) and non-advanced disease. There was a strong interaction, however, between one SNP in TAP (IVS11-896A>T, rs2299829) and the trial α-tocopherol supplement. Among men who were homozygous for the common allele, vitamin E supplementation was associated with an odds ratio (OR) for prostate cancer of 0.64 (95% confidence interval (CI): 0.46-0.88) and among those who carried the variant allele, the supplement was associated with an OR for prostate cancer of 1.20 (95% CI: 0.95-1.51) (p interaction = 0.002). There were significant but modest variations in baseline serum levels of α-tocopherol and serum responses to the vitamin E intervention for several of the SNPs examined. Conclusion : This study does not support an effect of these nine common polymorphisms in vitamin E transport genes on prostate cancer risk, but points to interactions with specific vitamin supplementation regimens that warrant further study.

[Fifth AACR International Conference on Frontiers in Cancer Prevention Research, Nov 12-15, 2006]