Hofmann JN, Yu K, Horst RL, Hayes RB, Purdue MPLong-term variation in serum 25-hydroxyvitamin D concentration among participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cancer Epidemiol Biomarkers Prev 19(4): 927-931

Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, EPS 8109, Bethesda, MD 20892-7240, USA.
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 03/2010; 19(4):927-31. DOI: 10.1158/1055-9965.EPI-09-1121
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Molecular epidemiologic studies of vitamin D and risk of cancer and other health outcomes usually involve a single measurement of the biomarker 25-hydroxyvitamin D [25(OH)D] in serum or plasma. However, the extent to which 25(OH)D concentration at a single time point is representative of an individual's long-term vitamin D status is unclear. To address this question, we evaluated within-person variability in 25(OH)D concentrations across serum samples collected at three time points over a 5-year period among 29 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Blood collection took place year-round, although samples for a given participant were collected in the same month each year. The within-person coefficient of variation and intraclass correlation coefficient were calculated using variance components estimated from random effects models. Spearman rank correlation coefficients were calculated to evaluate agreement between measurements at different collection times (baseline, +1 year, +5 years). The within-subject coefficient of variation was 14.9% [95% confidence interval (CI), 12.4-18.1%] and the intraclass correlation coefficient was 0.71 (95% CI, 0.63-0.88). Spearman rank correlation coefficients comparing baseline to +1 year, +1 year to +5 years, and baseline to +5 years were 0.65 (95% CI, 0.37-0.82), 0.61 (0.29-0.81), and 0.53 (0.17-0.77), respectively. Slightly stronger correlations were observed after restricting to non-Hispanic Caucasian subjects. These findings suggest that serum 25(OH)D concentration at a single time point may be a useful biomarker of long-term vitamin D status in population-based studies of various diseases.

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    • "Second, vitamin D status was assessed by a single measurement of serum 25(OH)D and can potentially result in misclassification of subjects' long-term vitamin D status. However, a recent study that analyzed serum 25(OH)D from the same individual at baseline, year-1 and year-5 observed relatively low within-subject variability and fairly high correlations in serum 25(OH)D measured at the three time points, suggesting serum 25(OH)D is reasonably stable over a long period of time [46]. When misclassification of vitamin D status using a single measurement is present, it is likely to be non-differential, which will result in bias towards the null. "
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    ABSTRACT: Background Vitamin D homeostasis may play a critical role in glucose metabolism. Little is known on vitamin D deficiency and its association with diabetes in countries of the Arabia Gulf where the population is experiencing a rapid increase in the incidence of diabetes. Methods In a cross-sectional study of 960 adults enrolled in the first National Nutrition Survey of the State of Kuwait (NNSSK), we examined vitamin D status in association with the prevalence of diabetes and prediabetes. Vitamin D status was measured by serum levels of 25-hydroxyvitami D (25(OH)D). Prevalences of diabetes and prediabetes were determined based on fasting glucose and HbA1C levels. Results The median level of serum 25(OH)D in Kuwaiti adults was 13.8 ng/ml. Approximately 56 % of the Kuwaiti adults had vitamin D inadequacy (25(OH)D = 12–19.9 ng/ml), and 27 % had vitamin D deficiency (25(OH)D < 12 ng/ml). The prevalences of prediabetes and diabetes were 40 and 27 %, respectively. Vitamin D inadequacy (OR = 1.7, 95 % CI: 1.0–2.9) and deficiency (OR =2.0, 95 % CI: 1.1–3.3) was each associated with about two-fold increased odds of prediabetes compared to sufficient vitamin D status (25(OH)D ≥20 ng/ml). Vitamin D inadequacy (OR =2.1, 95 % CI: 1.2–3.7) and deficiency (OR =2.0, 95 % CI: 1.1–3.9) were also associated with two-fold increased odds of diabetes. Conclusions Data from Kuwaiti’s first nutrition nutritional survey suggests a very high prevalence of vitamin D deficiency in Kuwaiti adults. Associations of low vitamin D status and high prevalence of diabetes point to the need of continuous monitoring of vitamin D status and further evaluating potential health consequences in this high-risk population.
    Preview · Article · Dec 2015 · BMC Public Health
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    • "Thus, our analytic approach of stratifying by DBP and examining the association between the 25(OH)D:DBP molar ratio and risk of bladder cancer are meaningful, albeit imperfect, proxies for calculated or measured free circulating 25(OH)D (Al-oanzi et al, 2006). Another potential limitation is our measurement of 25(OH)D and DBP at only one point in time, which may not be representative of the individual's usual vitamin D status, or their status during the aetiologically relevant time period; however, studies suggest that DBP levels are stable throughout adulthood (Haddad, 1995), and that circulating vitamin D levels measured up to 14 years apart are well correlated (Hofmann et al, 2010). Our study population consisted of male smokers, so it remains to be determined in future studies whether our findings can be generalised to women or non-smokers. "
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    ABSTRACT: Background: There is little research investigating the role of vitamin D binding protein (DBP) in the association between 25-hydroxyvitamin D (25(OH)D) and disease risk. Methods: Within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, 250 bladder cancer cases were randomly sampled and matched 1:1 to controls on age and date of blood collection. Odds ratios (OR) and 95% confidence intervals (CI) of bladder cancer were estimated by quartiles of DBP (measured by ELISA), 25(OH)D and the molar ratio of 25(OH)D:DBP, a proxy for free circulating 25(OH)D. Analyses were also conducted stratifying 25(OH)D by DBP (median split) and vice versa. Results: We found no direct association between circulating DBP levels and bladder cancer risk (P-trend=0.83). The inverse association between 25(OH)D and bladder cancer risk was unchanged after adjustment for DBP (Q4 vs Q1 OR=0.61, 95% CI=0.36–1.05; P-trend=0.04), and was stronger among men with lower DBP (low DBP: 25(OH)D Q4 vs Q1 OR=0.47, 95% CI=0.23–1.00; high DBP: 25(OH)D Q4 vs Q1 OR=0.83, 95% CI=0.40–1.75; P for interaction=0.11). Conclusion: Our findings provide additional support for an aetiologic role for vitamin D in bladder cancer and suggest that free, rather than total, circulating vitamin D may be a more relevant exposure when examining bladder and, perhaps, other cancers.
    Full-text · Article · Sep 2012 · British Journal of Cancer
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    • "We only used data from a single measurement of exposures which may be inadequate, [41] although a single measurement may be a useful biomarker of season-specific vitamin D status over a longer time. [42]. Our sample included mainly white children (the number of non-white children inthe main analyses was 84 (2.6%)), which may limit the generalisability of the results, but does mean that residual confounding due to ethnicity is unlikely. "
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    ABSTRACT: Non-clinical psychotic experiences are common and distressing. It has been hypothesized that early life vitamin D deficiency may be a risk factor for psychosis-related outcomes, but it is not known if circulating concentrations of 25-hydroxyvitamin D (25(OH)D) during childhood are associated with psychosis-related outcomes or whether the two different forms of 25(OH)D, (25(OH)D(3) and 25(OH)D(2), have similar associations with psychosis-related outcomes. We investigated the association between serum 25(OH)D(3) and 25(OH)D(2) concentrations and psychotic experiences in a prospective birth cohort study. Serum 25(OH)D(3) and 25(OH)D(2) concentrations were measured at mean age 9.8 years and psychotic experiences assessed at mean age 12.8 years by a psychologist (N = 3182). Higher 25(OH)D(3) concentrations were associated with lower risk of definite psychotic experiences (adjusted odds ratio: OR (95% confidence interval: CI) 0.85 (0.75-0.95)). Higher concentrations of 25(OH)D(2) were associated with higher risk of suspected and definite psychotic experiences (adjusted odds ratio: OR (95% confidence interval: CI) 1.26 (1.11, 1.43)). Higher 25(OD)D(2) concentrations were also weakly associated with definite psychotic experiences (adjusted OR (95% CI) 1.17 (0.96, 1.43), though with wide confidence intervals including the null value. Our findings of an inverse association of 25(OH)D(3) with definite psychotic experiences is consistent with the hypothesis that vitamin D may protect against psychosis-related outcomes.
    Full-text · Article · Jul 2012 · PLoS ONE
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