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Cancer Epidemiology, Biomarkers & Prevention
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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

Shaneda Warren Andersen, Xiao-Ou Shu, Qiuyin Cai, Nikhil K. Khankari, Mark D. Steinwandel, Peter W. Jurutka, William J. Blot and Wei Zheng
Shaneda Warren Andersen
1Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
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  • For correspondence: shaneda.n.warren.andersen@vanderbilt.edu
Xiao-Ou Shu
1Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
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Qiuyin Cai
1Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
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Nikhil K. Khankari
1Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
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Mark D. Steinwandel
2International Epidemiology Field Station, Vanderbilt Institute for Clinical and Translational Research, Rockville, Maryland.
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Peter W. Jurutka
3School of Mathematical and Natural Sciences, Arizona State University, Phoenix, Arizona.
4Department of Basic Medical Sciences, The University of Arizona, College of Medicine, Phoenix, Arizona.
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William J. Blot
1Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
2International Epidemiology Field Station, Vanderbilt Institute for Clinical and Translational Research, Rockville, Maryland.
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Wei Zheng
1Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
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DOI: 10.1158/1055-9965.EPI-17-0133 Published August 2017
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    Figure 1.

    Associations between free vitamin D and colorectal cancer risk by selected participant characteristics. Odds ratios are presented as a per standard deviation increase in level of free vitamin D and result from conditional logistic regression models where cases and controls are matched on race, age, and sex. Odds ratios and 95% confidence intervals are adjusted for calendar week of sample collection, body mass index, education, smoking, physical activity, alcohol intake, history of colorectal cancer screening, and family history of colorectal cancer. Analyses include African American cases with greater than 3 years between blood draw and diagnosis and their matched controls. Free vitamin D is calculated as 25(OH)D:VDBP molar ratio (×103) and is a proxy for free 25-hydroxyvitamin D status. a, P values for interaction were calculated by inclusion of cross-product terms for free vitamin D and the variable of interest. We were unable to calculate a P value for interaction between sex and free vitamin D status because sex was used as a matching factor.

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  • Table 1.

    Selected characteristics of African American participants at baseline by case status, SCCS, 2002–2009

    Baseline characteristics, N (%)Controls (N = 440)Cases (N = 224)
    Age, years, median (IQR)55 (13)55 (13)
    Male sex203 (46.1)100 (44.6)
    Education
     <High school163 (37.1)104 (46.4)
     High school147 (33.4)68 (30.4)
     >High school120 (27.3)47 (21.0)
    Household income, $
     <15,000275 (62.5)148 (66.1)
     15,000–49,999136 (30.9)67 (29.9)
     ≥50,00016 (3.6)2 (0.9)
    Colorectal cancer screening, ever121 (27.5)55 (24.6)
    Family history of colorectal cancer22 (5.0)12 (5.4)
    BMI, kg/m2, median (IQR)28.3 (9.9)29.4 (10.0)
    Current smoker184 (41.8)75 (33.5)
    Non- and moderate alcohol consumers337 (76.6)175 (78.1)
    Physical activity, MET-h/d, median (IQR)16.3 (22.7)15.9 (21.0)
    Sedentary time, hours, median (IQR)8.0 (6.2)8.0 (6.3)
    Total energy, kcal, median (IQR)2,212 (1748)2,261 (1826)
     Meat, servings/day, median (IQR)2 (2)2 (1)
     Fruits and vegetable, servings/day, median (IQR)3 (2)3 (2)
     Folate, micrograms/day, median (IQR)432 (373)471 (388)
    Vitamin D supplement use0 (0)0 (0)
     25-hydroxyvitamin D, ng/mL, median (IQR)13.0 (10.2)12.5 (10.7)
     Vitamin D–binding protein, μg/mL, median (IQR)300.6 (56.9)301.4 (62.2)
    • NOTE: Subjects with data missing for the characteristic of interest are not included in this analysis.

    • Abbreviation: IQR, interquartile range.

  • Table 2.

    Associations between vitamin D biomarkers and colorectal cancer risk, African American participants of the SCCS

    BiomarkerControlsCasesORa (95% CI)PtrendORb (95% CI)Ptrend
    25(OH)D, ng/mL
     Tertile 1: ≤10.49102711 (Ref)1 (Ref)
     Tertile 2: 10.50–16.08103470.65 (0.41–1.04)0.62 (0.38–1.01)
     Tertile 3: >16.08107570.77 (0.48–1.21)0.73 (0.45–1.17)
     Per standard deviation increase0.87 (0.71–1.06)0.170.82 (0.66–1.02)0.07
    VDBP, μg/mL
     Tertile 1: ≤280.20146741 (Ref)1 (Ref)
     Tertile 2: 280.21–320.00145690.93 (0.62–1.40)0.95 (0.63–1.45)
     Tertile 3: >320.00149811.10 (0.74–1.64)1.08 (0.72–1.63)
     Per standard deviation increase1.04 (0.88–1.23)0.661.03 (0.87–1.23)0.70
    Free 25(OH)Dc
     Tertile 1: ≤5.02103601 (Ref)1 (Ref)
     Tertile 2: 5.03–7.77102570.92 (0.57–1.46)0.85 (0.53–1.39)
     Tertile 3: >7.77107580.90 (0.56–1.44)0.83 (0.51–1.36)
     Per standard deviation increase0.87 (0.71–1.06)0.160.82 (0.66–1.01)0.07
    • Abbreviations: 25(OH)D, 25-hydroxyvitamin D; VDBP, vitamin D–binding protein; Ref, reference.

    • ↵aAnalyses result from conditional logistic regression models where cases and controls are matched on age, race, and sex. Analyses are adjusted for calendar week of sample collection, and body mass index.

    • ↵bIn addition, adjusted for education, smoking, physical activity, alcohol intake, history of colorectal cancer screening, and family history of colorectal cancer.

    • ↵cFree 25(OH)D biomarker is calculated as 25(OH)D:VDBP molar ratio (×103) and is a proxy for free 25-hydroxyvitamin D status.

  • Table 3.

    Associations between vitamin D biomarkers and colorectal cancer risk by time since blood draw, African American participants of the SCCS

    Time between blood draw and cancer diagnosis
    ≤3 years>3 years
    BiomarkerCasesORa (95% CI)PtrendCasesORa (95% CI)Ptrend
    25(OH)D, ng/mL
     Tertile 1: ≤10.49221 (Ref)491 (Ref)
     Tertile 2: 10.50–16.08281.22 (0.62–2.38)190.36 (0.19–0.69)
     Tertile 3: >16.08321.45 (0.75–2.79)250.45 (0.25–0.83)
     Per SD increase0.98 (0.76–1.28)0.900.69 (0.21–0.93)0.02
    VDBP, μg/mL
     Tertile 1: ≤280.20241 (Ref)501 (Ref)
     Tertile 2: 280.21–320.00251.08 (0.57–2.03)440.91 (0.56–1.48)
     Tertile 3: >320.00381.55 (0.86–2.82)430.85 (0.52–1.38)
     Per SD increase1.26 (1.00–1.60)0.050.89 (0.72–1.10)0.27
    Free 25(OH)Db
     Tertile 1: ≤5.02201 (Ref)401 (Ref)
     Tertile 2: 5.03–7.77291.38 (0.71–2.71)280.60 (0.33–1.09)
     Tertile 3: >7.77331.64 (0.83–3.23)250.51 (0.27–0.95)
     Per SD increase0.96 (0.74–1.25)0.760.71 (0.53–0.97)0.03
    • Abbreviations: 25(OH)D, 25-hydroxyvitamin D; VDBP, vitamin D–binding protein; Ref, reference; SD, standard deviation.

    • ↵aAnalyses result from conditional logistic regression models where cases and controls are matched on age, race, and sex. Analyses are adjusted for calendar week of sample collection, body mass index, education, smoking, physical activity, alcohol intake, history of colorectal cancer screening, and family history of colorectal cancer.

    • ↵bFree vitamin D biomarker is calculated as 25(OH)D:VDBP molar ratio (x103) and is a proxy for free 25-hydroxyvitamin D status.

Additional Files

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  • Supplementary Data

    • Table S1 - Associations between vitamin D biomarkers and colorectal cancer risk by time since blood draw, African American participants of the Southern Community Cohort Study.
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Cancer Epidemiology Biomarkers & Prevention: 26 (8)
August 2017
Volume 26, Issue 8
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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
Shaneda Warren Andersen, Xiao-Ou Shu, Qiuyin Cai, Nikhil K. Khankari, Mark D. Steinwandel, Peter W. Jurutka, William J. Blot and Wei Zheng
Cancer Epidemiol Biomarkers Prev August 1 2017 (26) (8) 1242-1247; DOI: 10.1158/1055-9965.EPI-17-0133

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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
Shaneda Warren Andersen, Xiao-Ou Shu, Qiuyin Cai, Nikhil K. Khankari, Mark D. Steinwandel, Peter W. Jurutka, William J. Blot and Wei Zheng
Cancer Epidemiol Biomarkers Prev August 1 2017 (26) (8) 1242-1247; DOI: 10.1158/1055-9965.EPI-17-0133
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