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 α-tocopherols [Ptrend < 0.01 for polynomial terms (3 df)]. The ORs (95% CI) for total tocopherols, which consisted primarily of α-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 α-tocopherol but nonsignificant for ß- and γ-tocopherol combined and for γ-tocopherol. Adjustment for serum lipids strengthened the nonlinear associations for total and α-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 µg/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.

Effects of calcium and vitamin D supplementation on blood pressure and serum lipids and carotenoids: a randomized, double-blind, placebo-controlled, clinical trial.

PURPOSE: To estimate the effects of calcium or vitamin D supplementation or a combination of both on blood pressure and serum lipid and carotenoid levels. METHODS: Ninety-two colorectal adenoma patients were randomized in a pilot, double-blind, placebo-controlled clinical trial of supplemental vitamin D3 800 IU and elemental calcium 2.0 g (as calcium carbonate) alone or in combination in divided doses twice daily with meals over 6 months. RESULTS: Relative to placebo, mean serum triglycerides decreased 30% (P = .10) and 32% (P = .10) in the calcium and calcium plus vitamin D3 treatment groups, respectively. When the two calcium intervention groups were pooled and compared with the pooled noncalcium groups, the estimated supplemental calcium treatment effects were statistically significant for triglycerides (P = .04). Similar but nonstatistically significant decreases (5%-7%) were observed for serum total cholesterol levels. Mean systolic blood pressure increased 6% (P = .08) in the calcium group; otherwise, there were no appreciable changes in systolic or diastolic blood pressures in any active treatment group. Mean serum total carotenoid levels decreased 14% (P = .07) in the calcium and 9% (P = .10) in the calcium plus vitamin D3 groups. CONCLUSIONS: Our results suggest that supplemental calcium alone or combined with vitamin D3 but not vitamin D3 alone may reduce serum lipids and lipophilic micronutrients.

C-reactive protein, lipid-soluble micronutrients, and survival in colorectal cancer patients.

BACKGROUND: Identification of biomarkers associated with survival in patients with cancer is important for elucidating the underlying mechanisms of cancer progression and identifying possible interventions to reduce cancer morbidity and mortality. METHODS: Using stored patient plasma samples from a multiethnic population-based case-control study of invasive colorectal cancer, we measured posttreatment blood levels of C-reactive protein (CRP) and lipid-soluble micronutrients. Patients (n = 368) were followed after phlebotomy (mean of 8 years), during which time 47% died (25% colorectal cancer specific). HRs were estimated by Cox proportional hazards regression with adjustment for stage, age at diagnosis, ethnicity, sex, smoking status, and month of blood draw. RESULTS: A positive association with overall risk of death was observed for CRP [HR for highest vs. lowest quintile: 1.80; 95% confidence interval (CI), 1.07-3.04; Ptrend = 0.01], whereas inverse associations were generally observed for retinol and carotenoids (HRs for overall risk of death for the highest quintile ranging from 0.5-0.8); these associations were significant for retinol (Ptrend = 0.0002), α-carotene (Ptrend = 0.02), and total carotenoids (Ptrend = 0.02) and were generally consistent across subgroups (sex, ethnicity, cancer anatomical subtype, and stage). HRs for retinol and carotenoids were attenuated somewhat after adjustment for CRP. Similar trends for CRP were observed for colorectal cancer-specific deaths (HR for highest vs. lowest tertile: 2.06; 95% CI, 1.18-3.61; Ptrend = 0.01) as for deaths from all other causes (Pheterogeneity = 0.78). CONCLUSIONS: These observations are consistent with a direct relationship between circulating CRP and overall survival among patients with colorectal cancer. IMPACT: These results, if reproduced, suggest that reduction of inflammation should be explored as a potential complementary treatment strategy.

Effects of vitamin D3 and calcium supplementation on serum levels of tocopherols, retinol, and specific vitamin D metabolites.

γ-Tocopherol (γT) protects against DNA-damaging effects of nitrogen oxides, yet its physiologic regulation in vivo is unknown. Observational studies indicate inverse associations of 25[OH]-vitamin D with γT and leptin. To determine whether vitamin D(3) supplementation alters levels of lipid-soluble micronutrients, serum samples (N = 85 subjects) from a randomized, double-blind, placebo-controlled clinical trial of vitamin D(3) (800 IU) and calcium (2 g), alone and in combination, were analyzed for lipid micronutrients and specific vitamin D metabolites at baseline and after 6 mo of supplementation. Serum 25[OH]-vitamin D(3) levels increased 55% (P < 0.0001) and 48% (P = 0.0005), whereas 25[OH]-vitamin D(2) levels were lower by 48% (P = 0.26) and 21% (P = 0.36) in the vitamin D(3) and vitamin D(3) plus calcium groups, respectively. At baseline, γT levels were inversely associated with 25[OH]D (r = -0.31, P = 0.004). With vitamin D(3) plus calcium treatment, serum α-tocopherol decreased 14% (P = 0.04), whereas similar changes in γT (19% lower, P = 0.14) were observed. No significant effects were observed for D(3) supplementation on leptin or retinol levels. These results are consistent with the hypothesis that vitamin D(3) ± calcium affects serum tocopherol and 25[OH]D(2) levels; however, studies using larger, more homogeneous populations are warranted.

Association of plasma micronutrient levels and urinary isoprostane with risk of lung cancer: the multiethnic cohort study.

Although smoking is the primary risk factor for lung cancer, there is evidence to suggest that fruit and vegetable intake are important cofactors. The present case-control study, nested within the Multiethnic Cohort Study, examined the associations of biomarkers of fruit and vegetable intake (individual plasma micronutrient levels), serum selenium, and a urinary biomarker for total lipid peroxidation with lung cancer risk. Two hundred seven incident cases were matched to 414 controls on age, sex, ethnicity, study location (Hawaii or California), smoking status, date/time of collection, and hours of fasting. We measured prediagnositic circulating levels of individual tocopherols and carotenoids, retinol, and serum selenium, and urinary 15-isoprostane F(2t). Conditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CI). For men, strong reductions in risk were seen with increasing tertiles of each plasma carotenoid, with the ORs for the third tertile, compared with the first tertile, ranging from 0.24 to 0.45 (P(trends), 0.002-0.04). No associations were found among women for carotenoids or among either sex for tocopherols, selenium, and retinol. A doubling in risk was seen for men in the second and third tertiles, compared with the first tertile of urinary 15-isoprostane F(2t) (OR, 2.31; 95% CI, 1.02-5.25; and OR, 2.16; 95% CI, 0.98-4.78). This study supports the previously observed association between circulating carotenoids and lung cancer risk in men, and adds to the limited literature regarding urinary 15-isoprostane F(2t) as a marker of cancer risk. Future research examining the possible relationship between isoprostanes and lung cancer is warranted.

Association of selenium, tocopherols, carotenoids, retinol, and 15-isoprostane F(2t) in serum or urine with prostate cancer risk: the multiethnic cohort.

OBJECTIVE: We examine the association of antioxidants and 15-isoprostane F(2t) with risk of prostate cancer. METHODS: We conducted a nested case-control study of serum antioxidant biomarkers (selenium, tocopherols, carotenoids, and retinol) and a urinary oxidation biomarker (15-isoprostane F(2t)) with risk of prostate cancer within the Multiethnic Cohort. Demographic, dietary, and other exposure information was collected by self-administered questionnaire in 1993-1996. We compared prediagnostic biomarker levels from 467 prostate cancer cases and 936 cancer free controls that were matched on several variables. Multivariate conditional logistic regression models were used to compute adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We observed that there was no overall association of serum concentrations of antioxidants and urinary concentrations of 15-isoprostane F(2t) with risk of prostate cancer or risk of advanced prostate cancer. However, we did observe an inverse association for serum selenium only among African-American men (p trend = 0.02); men in the third tertile of selenium concentrations had a 41% lower risk (95% CI: 0.38-0.93) of prostate cancer when compared to men in the first tertile. CONCLUSIONS: Overall, our study found no association of serum antioxidants or 15-isoprostane F(2t) with the risk of prostate cancer. The observed inverse association of selenium with prostate cancer in African-Americans needs to be validated in other studies.