\#947;-Tocopherol (\#947;T) is the primary tocopherol in the American diet and is found at micromolar levels in plasma, where it comprises 5-20% of tocopherols. \#947;T enhances cellular NO synthesis and protects cells from nitrogen oxide radical damage, and plasma and cellular \#947;T levels rise in response to inflammation. In addition, \#947;T and its metabolites possess anti-inflammatory properties, consequently, \#947;T may serve as the body's physiologic "aspirin" and represent a unique biomarker and mediator of pathological conditions associated with inflammation. Utilizing control subjects (n = 657) from a nested case-control study of prostate cancer (PC) in the Multiethnic Cohort, we assessed the association of \#947;T with antioxidant, metabolic, and inflammatory biomarkers in plasma. "Hyper \#947;-tocopherolemia", which we defined as plasma \#947;T levels >3 \#956;g/ml, was significantly inversely associated with plasma 25-OH vitamin D levels (Table 1). In hyper \#947;-tocopherolemic men, elevated median levels of coenzyme Q10 and C-reactive protein (37.5% higher; p = 0.01) were observed relative to those with normal \#947;T, whereas decreased plasma levels were observed for \#945;-tocopherol and the pro-vitamin A carotenoids, \#946;-carotene, \#945;-carotene and \#946;-cryptoxanthin (Table 1). In contrast, no significant differences in non pro-vtamin A carotenoids were observed. Hyper \#947;-tocopherolemic men were more likely to die of all causes (OR = 2.475: p = 0.0097) relative to men with normal \#947;T levels (< 3 \#956;g/ml). In comparison, hyper-cholesterolemic subjects (> 220 mg/dL) were not at significantly elevated risk of dying (OR = 1.273; p = 0.562), suggesting that elevated \#947;T may be superior to cholesterol as a risk marker for all-cause mortality, however, the mortality association should be replicated in larger studies. Possible mechanistic explanations for the observed associations and their implications are discussed. $$table_{D00F26E4-4957-4B32-B1F2-44E3792E73AA}$$

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3899.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO