title: Supplementation with alpha-tocopherol or beta-carotene reduces serum concentrations of vascular endothelial growth factor-D, but Not -A or -C, in male smokers.
abstract: Evidence from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study suggests that vitamin E and β-carotene supplement use may influence the risk of several cancers. Vascular endothelial growth factors (VEGF) are proteins involved in angiogenesis, an important requirement for tumor growth and metastasis. Thus, vitamin E and β-carotene may influence cancer risk through one or more VEGF. The ATBC Study was a randomized, double-blind, placebo-controlled, primary cancer prevention trial in which participants were assigned to 1 of 4 supplementation groups based on a 2 × 2 factorial design: 1) α-tocopherol (vitamin E); 2) β-carotene; 3) both; or 4) placebo. For the present study, 100 cancer-free participants with follow-up serum available were randomly selected from each intervention group. VEGF-A, -C, and -D concentrations were measured by ELISA in serum obtained at baseline and after at least 2 y of supplementation. Differences in change in VEGF levels from baseline to follow-up between intervention groups were assessed using the ANOVA test. Change in VEGF-A and VEGF-C concentrations between baseline and follow-up did not differ by intervention group (P = 0.45 and 0.29, respectively). The decrease in the serum VEGF-D concentration was greater in the men supplemented with α-tocopherol (-9.7 ± 2.5%) or β-carotene (-8.5 ± 2.7%) and tended to be greater in those supplemented with both (-6.8 ± 2.4%) compared to the placebo group, in which there was no change (-0.4 ± 3.0%) (P = 0.03). In this population of male smokers, supplementation with α-tocopherol or β-carotene was associated with a decrease in VEGF-D levels over time. Although the mechanism through which these supplements affect cancer etiolog remains unclear, our results support the hypothesis that vitamin E and β-carotene may influence cancer progression through VEGF-mediated lymphangiogenesis.
authors.affiliation: Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA. mondulam@mail.nih.gov
authors.forename: Alison M
authors.initials: AM
authors.lastname: Mondul
authors.forename: Helen C
authors.initials: HC
authors.lastname: Rager
authors.forename: William
authors.initials: W
authors.lastname: Kopp
authors.forename: Jarmo
authors.initials: J
authors.lastname: Virtamo
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
mesh_terms: D019587:Dietary Supplements; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D010919:Placebos; D012907:Smoking / Q000097:blood*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D042582:Vascular Endothelial Growth Factor C / Q000097:blood*; D042643:Vascular Endothelial Growth Factor D / Q000097:blood*; D024502:alpha-Tocopherol / Q000008:administration & dosage*; D019207:beta Carotene / Q000008:administration & dosage*
chemical_list: D010919:Placebos; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D019207:beta Carotene; D024502:alpha-Tocopherol