Prediagnostic Serum Tocopherol Levels and the Risk of Non-Hodgkin Lymphoma: The Multiethnic Cohort

Background: Compromised immunity and chronic inflammation are thought to contribute to the development of non-Hodgkin lymphoma (NHL). Because tocopherols protect cells through antioxidant mechanisms, they may play a role in NHL etiology. Methods: This nested case-control study within the Multiethnic Cohort examined the association of prediagnostic serum tocopherols levels measured in 271 NHL cases and 538 matched controls by high-pressure liquid chromatography/photodiode array detection with NHL risk. Conditional logistic regression was used to calculate ORs and 95% confidence intervals (CI). Results: We observed U-shaped associations with NHL for total and alpha-tocopherols [P-trend < 0.01 for polynomial terms (3 df)]. The ORs (95% CI) for total tocopherols, which consisted primarily of alpha-tocopherol, were 0.41 (0.25-0.68), 0.52 (0.32-0.85), 0.39 (0.23-0.65), and 0.78 (0.47-1.29) for the second to fifth quintiles as compared with the first. The risk estimates were similar for alpha-tocopherol but nonsignificant for beta- and gamma-tocopherol combined and for gamma-tocopherol. Adjustment for serum lipids strengthened the nonlinear associations for total and alpha-tocopherols. Serum total tocopherol levels were higher for vitamin E supplement users at cohort entry than nonusers (21.32 +/- 9.04 vs. 17.72 +/- 7.43 mu g/mL; P < 0.0001), but supplement use was not associated with NHL risk. No heterogeneity in risk estimates was detected by sex, ethnicity, vitamin E supplement use, or NHL subtype. Conclusions: Circulating tocopherols, at levels likely reflecting adequate dietary intakes, may be protective against NHL, whereas higher intakes from supplementation may not be beneficial. Impact: The association between serum tocopherol levels and NHL risk provides possible new insights into the etiology of NHL. (C) 2013 AACR.