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Serum 25-Hydroxyvitamin D Concentrations ?40 ng/ml Are Associated with >65% Lower Cancer Risk: Pooled Analysis of Randomized Trial and Prospective Cohort Study.

ABSTRACT: Higher serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with a lower risk of multiple cancer types across a range of 25(OH)D concentrations.To investigate whether the previously reported inverse association between 25(OH)D and cancer risk could be replicated, and if a 25(OH)D response region could be identified among women aged 55 years and older across a broad range of 25(OH)D concentrations.Data from two cohorts representing different median 25(OH)D concentrations were pooled to afford a broader range of 25(OH)D concentrations than either cohort alone: the Lappe cohort (N = 1,169), a randomized clinical trial cohort (median 25(OH)D = 30 ng/ml) and the GrassrootsHealth cohort (N = 1,135), a prospective cohort (median 25(OH)D = 48 ng/ml). Cancer incidence over a multi-year period (median: 3.9 years) was compared according to 25(OH)D concentration. Kaplan-Meier plots were developed and the association between 25(OH)D and cancer risk was examined with multivariate Cox regression using multiple 25(OH)D measurements and spline functions. The study included all invasive cancers excluding skin cancer.Age-adjusted cancer incidence across the combined cohort (N = 2,304) was 840 cases per 100,000 person-years (1,020 per 100,000 person-years in the Lappe cohort and 722 per 100,000 person-years in the GrassrootsHealth cohort). Incidence was lower at higher concentrations of 25(OH)D. Women with 25(OH)D concentrations ?40 ng/ml had a 67% lower risk of cancer than women with concentrations <20 ng/ml (HR = 0.33, 95% CI = 0.12-0.90).25(OH)D concentrations ?40 ng/ml were associated with substantial reduction in risk of all invasive cancers combined.

SUBMITTER: McDonnell SL

PROVIDER: S-EPMC4822815 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Serum 25-Hydroxyvitamin D Concentrations ≥40 ng/ml Are Associated with >65% Lower Cancer Risk: Pooled Analysis of Randomized Trial and Prospective Cohort Study.

McDonnell Sharon L SL Baggerly Carole C French Christine B CB Baggerly Leo L LL Garland Cedric F CF Gorham Edward D ED Lappe Joan M JM Heaney Robert P RP

PloS one 20160406 4

<h4>Background</h4>Higher serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with a lower risk of multiple cancer types across a range of 25(OH)D concentrations.<h4>Objectives</h4>To investigate whether the previously reported inverse association between 25(OH)D and cancer risk could be replicated, and if a 25(OH)D response region could be identified among women aged 55 years and older across a broad range of 25(OH)D concentrations.<h4>Methods</h4>Data from two cohorts repre ...[more]

PMID: 27049526

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Project description:BACKGROUND:While numerous epidemiologic studies have found an association between higher serum 25-hydroxyvitamin D [25(OH)D] concentrations and lower breast cancer risk, few have assessed this association for concentrations >40 ng/ml. OBJECTIVE:To investigate the relationship between 25(OH)D concentration and breast cancer risk across a broad range of 25(OH)D concentrations among women aged 55 years and older. METHODS:Analyses used pooled data from two randomized clinical trials (N = 1129, N = 2196) and a prospective cohort (N = 1713) to examine a broad range of 25(OH)D concentrations. The outcome was diagnosis of breast cancer during the observation periods (median: 4.0 years). Three analyses were conducted: 1) Incidence rates were compared according to 25(OH)D concentration from <20 to ?60 ng/ml (<50 to ?150 nmol/L), 2) Kaplan-Meier plots were developed and 3) multivariate Cox regression was used to examine the association between 25(OH)D and breast cancer risk using multiple 25(OH)D measurements. RESULTS:Within the pooled cohort (N = 5038), 77 women were diagnosed with breast cancer (age-adjusted incidence: 512 cases per 100,000 person-years). Results were similar for the three analyses. First, comparing incidence rates, there was an 82% lower incidence rate of breast cancer for women with 25(OH)D concentrations ?60 vs <20 ng/ml (Rate Ratio = 0.18, P = 0.006). Second, Kaplan-Meier curves for concentrations of <20, 20-39, 40-59 and ?60 ng/ml were significantly different (P = 0.02), with the highest proportion breast cancer-free in the ?60 ng/ml group (99.3%) and the lowest proportion breast cancer-free in the <20 ng/ml group (96.8%). The proportion with breast cancer was 78% lower for ?60 vs <20 ng/ml (P = 0.02). Third, multivariate Cox regression revealed that women with 25(OH)D concentrations ?60 ng/ml had an 80% lower risk of breast cancer than women with concentrations <20 ng/ml (HR = 0.20, P = 0.03), adjusting for age, BMI, smoking status, calcium supplement intake, and study of origin. CONCLUSIONS:Higher 25(OH)D concentrations were associated with a dose-response decrease in breast cancer risk with concentrations ?60 ng/ml being most protective.

Project description:Gallbladder mucocele (GBM) is a common biliary disorder in dogs. Gallbladder hypokinesia has been proposed to contribute to its formation and progression. The specific cause of gallbladder stasis in dogs with GBM as well as viable treatment options to resolve dysmotility remains unknown. Vitamin D deficiency is one of the many potential causes of gallbladder hypokinesia in humans and repletion results in complete resolution of stasis. Improving our understanding of the relationship between serum vitamin D and GBM could help identify dogs as a model for humans with gallbladder hypokinesia. Furthermore, this relationship could provide insight into the pathogenesis of GBM and support the need for future studies to investigate vitamin D as a novel treatment target. Therefore, goals of this study were i) to determine if serum 25-hydroxyvitamin(OH)D concentrations were decreased in dogs with GBM, ii) if serum 25(OH)D concentrations were different in clinical versus dogs subclinical for GBM, and iii) to determine if serum 25(OH)D concentrations could predict the ultrasonographic type of GBM. Sixty-two dogs (clinical, n = 26; subclinical, n = 36) with GBM and 20 healthy control dogs were included in this prospective observational study. Serum 25(OH)D concentrations were measured with a competitive chemiluminescence immunoassay. Overall, dogs with GBM had lower serum 25(OH)D concentrations than control dogs (P = 0.004). Subsequent subgroup analysis indicated that this difference was only significant in the subclinical group compared to the control dogs (P = 0.008), and serum 25(OH)D concentrations did not significantly differ between dogs clinical for GBM versus subclinical or control dogs, indicating that inflammatory state in clinical dogs was not the major constituent of the observed findings. Decreasing serum 25(OH)D concentrations, but not clinical status, was associated with a more advanced developmental stage of GBM type determined by ultrasonography. Our results indicate that vitamin D has a role in dogs with GBM. Additional studies are needed to assess if reduced vitamin D in dogs with GBM is a cause or effect of their biliary disease and to investigate if vitamin D supplementation could be beneficial for dogs with GBM.

Dataset Information

Serum 25-Hydroxyvitamin D Concentrations ?40 ng/ml Are Associated with >65% Lower Cancer Risk: Pooled Analysis of Randomized Trial and Prospective Cohort Study.

Publications

Serum 25-Hydroxyvitamin D Concentrations ≥40 ng/ml Are Associated with >65% Lower Cancer Risk: Pooled Analysis of Randomized Trial and Prospective Cohort Study.

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