“ Vitamin E is an important antioxidant that prevents free radical reactions and lipid peroxidation. It is this oxidative stress preventing function that may be particularly relevant in relation to the development of several cancers, including prostate. However, a major controversy over the association of vitamin E with prostate cancer risk prevails, because a beneficial effect of vitamin E supplements was found in a randomized controlled trial of smokers (1) but not in two other trials not specifically recruiting smokers (2, 3). Whether the beneficial association exists only among smokers or other factors, such as genetic polymorphisms related to oxidative stress, play a role is inconclusive. A hypothesized mechanism of oxidative stress in relation to prostate cancer involves four important enzymes: MnSOD8, GPX1, CAT, and MPO.
The primary objective of this new study (4) was to examine associations of serum alpha- and gamma-tocopherol with prostate cancer risk in the randomized controlled CARET trial (5), using a nested case-control study design. Alpha- and gamma-tocopherol concentrations were assayed among 684 male heavy smokers and asbestos-exposed workers with incident prostate cancer and 1441 controls. We further investigated whether the genetic variants (polymorphisms) in the four selected oxidative stress regulatory enzymes, MnSOD, GPX1, CAT, and MPO, modified these associations.
The study results showed that
- Higher serum alpha- and gamma-tocopherol concentrations were associated with reduced risks of aggressive prostate cancer among current smokers.
- Current smokers with the highest serum concentrations of alpha-tocopherol had a 38% decreased risk of prostate cancer compared to those with the lowest concentrations.
- Participants with the highest serum gamma-tocopherol concentrations had a non-significant, 31% reduced risk of aggressive prostate cancer.
- Genetic variations in the oxidative stress regulatory enzyme MPO were associated with a nearly two-fold increased risk of aggressive prostate cancer among current smokers with low serum alpha-tocopherol levels.
In conclusion, our data suggest that, among current smokers, high serum alpha- and gamma-tocopherol concentrations are associated with reduced risks of aggressive prostate cancer. High serum alpha-tocopherol concentrations may be particularly important among men with genetic variation in MPO in reducing prostate cancer risk. As the MPO variations were present in 40% of our study population, our observations are important from a public health perspective, because these genotypes are not rare in the general population.”
Washington, July 2011
Addendum: Past studies which failed to find a protective benefit of vitamin E supplementation on prostate cancer risk did not consider the potential effect of genetic polymorphisms on vitamin E metabolism. Genetic polymorphisms seem to be relevant for micronutrient efficacy: vitamin E, for example, provides cardiovascular protection to individuals with diabetes and a certain haptoglobin (HP 2-2) genotype (6). Re-evaluations of two trials (HOPE and ICARE) found that vitamin E supplementation (400 IU daily) significantly decreased risk of cardiovascular death and myocardial infarction in individuals with diabetes mellitus and the HP 2-2 genotype (7). Given that Americans 2 years and older are consuming only 7.7 mg vitamin E daily (8) – about half of the recommended 15 mg per day – dietary supplementation may be beneficial.