Dataset Information

Total and Free Circulating Vitamin D and Vitamin D-Binding Protein in Relation to Colorectal Cancer Risk in a Prospective Study of African Americans.

ABSTRACT: Background: Previous studies rarely evaluated the associations between vitamin D-binding protein and free vitamin D with colorectal cancer risk. We assessed these biomarkers and total 25-hydroxyvitamin D in relation to colorectal cancer risk in a sample of African Americans.Methods: Cases comprised 224 African American participants of the Southern Community Cohort Study diagnosed with incident colorectal cancer. Controls (N = 440) were selected through incidence density sampling and matched to cases on age, sex, and race. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for associations between biomarker levels and colorectal cancer risk.Results: Vitamin D was inversely associated with colorectal cancer risk where the OR per-SD increase in total and free 25-hydroxyvitamin D were 0.82 (95% CI, 0.66-1.02) and 0.82 (95% CI, 0.66-1.01), respectively. Associations were most apparent among cases diagnosed >3 years after blood draw: ORs for the highest tertile versus the lowest were 0.69 (95% CI, 0.21-0.93) for total 25-hydroxyvitamin D and 0.71 (95% CI, 0.53-0.97) for free 25-hydroxyvitamin D. Inverse associations were seen in strata defined by sex, BMI, and anatomic site, although not all findings were statistically significant. Vitamin D-binding protein was not associated with colorectal cancer risk.Conclusions: Our findings suggest that total and free 25-hydroxyvitamin D may be inversely associated with colorectal cancer risk among African Americans.Impact: These findings highlight a potential role for vitamin D in colorectal cancer prevention in African Americans. Cancer Epidemiol Biomarkers Prev; 26(8); 1242-7. ©2017 AACR.

SUBMITTER: Andersen SW

PROVIDER: S-EPMC5540758 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Total and Free Circulating Vitamin D and Vitamin D-Binding Protein in Relation to Colorectal Cancer Risk in a Prospective Study of African Americans.

Andersen Shaneda Warren SW Shu Xiao-Ou XO Cai Qiuyin Q Khankari Nikhil K NK Steinwandel Mark D MD Jurutka Peter W PW Blot William J WJ Zheng Wei W

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20170508 8

Background: Previous studies rarely evaluated the associations between vitamin D-binding protein and free vitamin D with colorectal cancer risk. We assessed these biomarkers and total 25-hydroxyvitamin D in relation to colorectal cancer risk in a sample of African Americans.Methods: Cases comprised 224 African American participants of the Southern Community Cohort Study diagnosed with incident colorectal cancer. Controls (N = 440) were selected through incidence density samp ...[more]

PMID: 28483970

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Project description:BACKGROUND:Low levels of total 25-hydroxyvitamin D are common among black Americans. Vitamin D-binding protein has not been considered in the assessment of vitamin D deficiency. METHODS:In the Healthy Aging in Neighborhoods of Diversity across the Life Span cohort of blacks and whites (2085 participants), we measured levels of total 25-hydroxyvitamin D, vitamin D-binding protein, and parathyroid hormone as well as bone mineral density (BMD). We genotyped study participants for two common polymorphisms in the vitamin D-binding protein gene (rs7041 and rs4588). We estimated levels of bioavailable 25-hydroxyvitamin D in homozygous participants. RESULTS:Mean (±SE) levels of both total 25-hydroxyvitamin D and vitamin D-binding protein were lower in blacks than in whites (total 25-hydroxyvitamin D, 15.6±0.2 ng per milliliter vs. 25.8±0.4 ng per milliliter, P<0.001; vitamin D-binding protein, 168±3 ?g per milliliter vs. 337±5 ?g per milliliter, P<0.001). Genetic polymorphisms independently appeared to explain 79.4% and 9.9% of the variation in levels of vitamin D-binding protein and total 25-hydroxyvitamin D, respectively. BMD was higher in blacks than in whites (1.05±0.01 g per square centimeter vs. 0.94±0.01 g per square centimeter, P<0.001). Levels of parathyroid hormone increased with decreasing levels of total or bioavailable 25-hydroxyvitamin D (P<0.001 for both relationships), yet within each quintile of parathyroid hormone concentration, blacks had significantly lower levels of total 25-hydroxyvitamin D than whites. Among homozygous participants, blacks and whites had similar levels of bioavailable 25-hydroxyvitamin D overall (2.9±0.1 ng per milliliter and 3.1±0.1 ng per milliliter, respectively; P=0.71) and within quintiles of parathyroid hormone concentration. CONCLUSIONS:Community-dwelling black Americans, as compared with whites, had low levels of total 25-hydroxyvitamin D and vitamin D-binding protein, resulting in similar concentrations of estimated bioavailable 25-hydroxyvitamin D. Racial differences in the prevalence of common genetic polymorphisms provide a likely explanation for this observation. (Funded by the National Institute on Aging and others.).

Project description:This review focuses on the biologic importance of the vitamin D binding protein (DBP) with emphasis on its regulation of total and free vitamin D metabolite levels in various clinical conditions. Nearly all DBP is produced in the liver, where its regulation is influenced by estrogen, glucocorticoids and inflammatory cytokines but not by vitamin D itself. DBP is the most polymorphic protein known, and different DBP alleles can have substantial impact on its biologic functions. The three most common alleles-Gc1f, Gc1s, Gc2-differ in their affinity with the vitamin D metabolites and have been variably associated with a number of clinical conditions. Although DBP has a number of biologic functions independent of vitamin D, its major biologic function is that of regulating circulating free and total levels of vitamin D metabolites. 25 hydroxyvitamin D (25(OH)D) is the best studied form of vitamin D as it provides the best measure of vitamin D status. In a normal non-pregnant individual, approximately 0.03% of 25(OH)D is free; 85% is bound to DBP, 15% is bound to albumin. The free hormone hypothesis postulates that only free 25(OH)D can enter cells. This hypothesis is supported by the observation that mice lacking DBP, and therefore with essentially undetectable 25(OH)D levels, do not show signs of vitamin D deficiency unless put on a vitamin D deficient diet. Similar observations have recently been described in a family with a DBP mutation. This hypothesis also applies to other protein bound lipophilic hormones including glucocorticoids, sex steroids, and thyroid hormone. However, tissues expressing the megalin/cubilin complex, such as the kidney, have the capability of taking up 25(OH)D still bound to DBP, but most tissues rely on the free level. Attempts to calculate the free level using affinity constants generated in a normal individual along with measurement of DBP and total 25(OH)D have not accurately reflected directly measured free levels in a number of clinical conditions. In this review, we examine the impact of different clinical conditions as well as different DBP alleles on the relationship between total and free 25(OH)D, using only data in which the free 25(OH)D level was directly measured. The major conclusion is that a number of clinical conditions alter this relationship, raising the question whether measuring just total 25(OH)D might be misleading regarding the assessment of vitamin D status, and such assessment might be improved by measuring free 25(OH)D instead of or in addition to total 25(OH)D.

Dataset Information

Total and Free Circulating Vitamin D and Vitamin D-Binding Protein in Relation to Colorectal Cancer Risk in a Prospective Study of African Americans.

Publications

Total and Free Circulating Vitamin D and Vitamin D-Binding Protein in Relation to Colorectal Cancer Risk in a Prospective Study of African Americans.

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