Association of Circulating Vitamin D With Colorectal Cancer Depends on Vitamin D-Binding Protein Isoforms: A Pooled, Nested, Case-Control Study

David Corley Gibbs; Mingyang Song; Marjorie L McCullough; Caroline Y Um; Roberd M Bostick; Kana Wu; W Dana Flanders; Edward Giovannucci; Mazda Jenab; Magritt Brustad; Anne Tjønneland; Aurora Perez-Cornago; Antonia Trichopoulou; Konstantinos K Tsilidis; Johan Hultdin; Aurelio Barricarte Gurrea; Bas Bueno-de-Mesquita; Yahya Mahamat-Saleh; Tilman Kühn; Marc J Gunter; Elisabete Weiderpass; Veronika Fedirko

doi:10.1093/jncics/pkz083

Association of Circulating Vitamin D With Colorectal Cancer Depends on Vitamin D-Binding Protein Isoforms: A Pooled, Nested, Case-Control Study

David Corley Gibbs, Mingyang Song, Marjorie L McCullough, Caroline Y Um, Roberd M Bostick, Kana Wu, W Dana Flanders, Edward Giovannucci, Mazda Jenab, Magritt Brustad, Anne Tjønneland, Aurora Perez-Cornago, Antonia Trichopoulou, Konstantinos K Tsilidis, Johan Hultdin, Aurelio Barricarte Gurrea, Bas Bueno-de-Mesquita, Yahya Mahamat-Saleh, Tilman Kühn, Marc J GunterElisabete Weiderpass, Veronika Fedirko

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Background: Higher circulating 25-hydroxyvitamin-D [25(OH)D] concentrations are consistently inversely associated with colorectal cancer (CRC) risk in observational studies. However, it is unknown whether this association depends on the functional GC-rs4588*A (Thr436Lys) variant encoding the vitamin D-binding protein-2 (DBP2) isoform, which may affect vitamin D status and bioavailability.

Methods: We analyzed data from 1710 incident CRC cases and 1649 incidence-density-matched controls nested within three prospective cohorts of mostly Caucasians. Study-specific incidence rate ratios (RRs) for associations of prediagnostic, season-standardized 25(OH)D concentrations according to DBP2 isoform with CRC were estimated using multivariable unconditional logistic regression and were pooled using fixed-effects models. All statistical significance tests were two-sided.

Results: The odds of having 25(OH)D concentrations less than 50 nmol/L (considered insufficient by the Institute of Medicine) were 43% higher for each DBP2-encoding variant (rs4588*A) inherited (per DBP2 odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.27 to 1.62, Ptrend = 1.2 × 10-8). The association of 25(OH)D concentrations with CRC risk differed by DBP2: 25(OH)D concentrations considered sufficient (≥ 50 nmol/L), relative to deficient (< 30 nmol/L), were associated with a 53% lower CRC risk among individuals with the DBP2 isoform (RR = 0.47, 95% CI = 0.33 to 0.67), but with a non-statistically significant 12% lower risk among individuals without it (RR = 0.88, 95% CI = 0.61 to 1.27) (Pheterogeneity = .01).

Conclusions: Our results suggest that the 25(OH)D-CRC association may differ by DBP isoform, and those with a DBP2-encoding genotype linked to vitamin D insufficiency may particularly benefit from adequate 25(OH)D for CRC prevention.

Original language	English (US)
Pages (from-to)	pkz083
Journal	JNCI Cancer Spectrum
Volume	4
Issue number	1
DOIs	https://doi.org/10.1093/jncics/pkz083
State	Published - Feb 2020
Externally published	Yes

Access to Document

10.1093/jncics/pkz083

Cite this

Gibbs, D. C., Song, M., McCullough, M. L., Um, C. Y., Bostick, R. M., Wu, K., Flanders, W. D., Giovannucci, E., Jenab, M., Brustad, M., Tjønneland, A., Perez-Cornago, A., Trichopoulou, A., Tsilidis, K. K., Hultdin, J., Barricarte Gurrea, A., Bueno-de-Mesquita, B., Mahamat-Saleh, Y., Kühn, T., ... Fedirko, V. (2020). Association of Circulating Vitamin D With Colorectal Cancer Depends on Vitamin D-Binding Protein Isoforms: A Pooled, Nested, Case-Control Study. JNCI Cancer Spectrum, 4(1), pkz083. https://doi.org/10.1093/jncics/pkz083

Gibbs, DC, Song, M, McCullough, ML, Um, CY, Bostick, RM, Wu, K, Flanders, WD, Giovannucci, E, Jenab, M, Brustad, M, Tjønneland, A, Perez-Cornago, A, Trichopoulou, A, Tsilidis, KK, Hultdin, J, Barricarte Gurrea, A, Bueno-de-Mesquita, B, Mahamat-Saleh, Y, Kühn, T, Gunter, MJ, Weiderpass, E & Fedirko, V 2020, 'Association of Circulating Vitamin D With Colorectal Cancer Depends on Vitamin D-Binding Protein Isoforms: A Pooled, Nested, Case-Control Study', JNCI Cancer Spectrum, vol. 4, no. 1, pp. pkz083. https://doi.org/10.1093/jncics/pkz083

@article{520fb7fd1e064f2da9d50ca03fabf541,

title = "Association of Circulating Vitamin D With Colorectal Cancer Depends on Vitamin D-Binding Protein Isoforms: A Pooled, Nested, Case-Control Study",

abstract = "Background: Higher circulating 25-hydroxyvitamin-D [25(OH)D] concentrations are consistently inversely associated with colorectal cancer (CRC) risk in observational studies. However, it is unknown whether this association depends on the functional GC-rs4588*A (Thr436Lys) variant encoding the vitamin D-binding protein-2 (DBP2) isoform, which may affect vitamin D status and bioavailability.Methods: We analyzed data from 1710 incident CRC cases and 1649 incidence-density-matched controls nested within three prospective cohorts of mostly Caucasians. Study-specific incidence rate ratios (RRs) for associations of prediagnostic, season-standardized 25(OH)D concentrations according to DBP2 isoform with CRC were estimated using multivariable unconditional logistic regression and were pooled using fixed-effects models. All statistical significance tests were two-sided.Results: The odds of having 25(OH)D concentrations less than 50 nmol/L (considered insufficient by the Institute of Medicine) were 43% higher for each DBP2-encoding variant (rs4588*A) inherited (per DBP2 odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.27 to 1.62, Ptrend = 1.2 × 10-8). The association of 25(OH)D concentrations with CRC risk differed by DBP2: 25(OH)D concentrations considered sufficient (≥ 50 nmol/L), relative to deficient (< 30 nmol/L), were associated with a 53% lower CRC risk among individuals with the DBP2 isoform (RR = 0.47, 95% CI = 0.33 to 0.67), but with a non-statistically significant 12% lower risk among individuals without it (RR = 0.88, 95% CI = 0.61 to 1.27) (Pheterogeneity = .01).Conclusions: Our results suggest that the 25(OH)D-CRC association may differ by DBP isoform, and those with a DBP2-encoding genotype linked to vitamin D insufficiency may particularly benefit from adequate 25(OH)D for CRC prevention.",

author = "Gibbs, {David Corley} and Mingyang Song and McCullough, {Marjorie L} and Um, {Caroline Y} and Bostick, {Roberd M} and Kana Wu and Flanders, {W Dana} and Edward Giovannucci and Mazda Jenab and Magritt Brustad and Anne Tj{\o}nneland and Aurora Perez-Cornago and Antonia Trichopoulou and Tsilidis, {Konstantinos K} and Johan Hultdin and {Barricarte Gurrea}, Aurelio and Bas Bueno-de-Mesquita and Yahya Mahamat-Saleh and Tilman K{\"u}hn and Gunter, {Marc J} and Elisabete Weiderpass and Veronika Fedirko",

note = "{\textcopyright} The Author(s) 2020. Published by Oxford University Press.",

year = "2020",

month = feb,

doi = "10.1093/jncics/pkz083",

language = "English (US)",

volume = "4",

pages = "pkz083",

journal = "JNCI Cancer Spectrum",

issn = "2515-5091",

publisher = "Oxford University Press",

number = "1",

}

TY - JOUR

T1 - Association of Circulating Vitamin D With Colorectal Cancer Depends on Vitamin D-Binding Protein Isoforms

T2 - A Pooled, Nested, Case-Control Study

AU - Gibbs, David Corley

AU - Song, Mingyang

AU - McCullough, Marjorie L

AU - Um, Caroline Y

AU - Bostick, Roberd M

AU - Wu, Kana

AU - Flanders, W Dana

AU - Giovannucci, Edward

AU - Jenab, Mazda

AU - Brustad, Magritt

AU - Tjønneland, Anne

AU - Perez-Cornago, Aurora

AU - Trichopoulou, Antonia

AU - Tsilidis, Konstantinos K

AU - Hultdin, Johan

AU - Barricarte Gurrea, Aurelio

AU - Bueno-de-Mesquita, Bas

AU - Mahamat-Saleh, Yahya

AU - Kühn, Tilman

AU - Gunter, Marc J

AU - Weiderpass, Elisabete

AU - Fedirko, Veronika

PY - 2020/2

Y1 - 2020/2

N2 - Background: Higher circulating 25-hydroxyvitamin-D [25(OH)D] concentrations are consistently inversely associated with colorectal cancer (CRC) risk in observational studies. However, it is unknown whether this association depends on the functional GC-rs4588*A (Thr436Lys) variant encoding the vitamin D-binding protein-2 (DBP2) isoform, which may affect vitamin D status and bioavailability.Methods: We analyzed data from 1710 incident CRC cases and 1649 incidence-density-matched controls nested within three prospective cohorts of mostly Caucasians. Study-specific incidence rate ratios (RRs) for associations of prediagnostic, season-standardized 25(OH)D concentrations according to DBP2 isoform with CRC were estimated using multivariable unconditional logistic regression and were pooled using fixed-effects models. All statistical significance tests were two-sided.Results: The odds of having 25(OH)D concentrations less than 50 nmol/L (considered insufficient by the Institute of Medicine) were 43% higher for each DBP2-encoding variant (rs4588*A) inherited (per DBP2 odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.27 to 1.62, Ptrend = 1.2 × 10-8). The association of 25(OH)D concentrations with CRC risk differed by DBP2: 25(OH)D concentrations considered sufficient (≥ 50 nmol/L), relative to deficient (< 30 nmol/L), were associated with a 53% lower CRC risk among individuals with the DBP2 isoform (RR = 0.47, 95% CI = 0.33 to 0.67), but with a non-statistically significant 12% lower risk among individuals without it (RR = 0.88, 95% CI = 0.61 to 1.27) (Pheterogeneity = .01).Conclusions: Our results suggest that the 25(OH)D-CRC association may differ by DBP isoform, and those with a DBP2-encoding genotype linked to vitamin D insufficiency may particularly benefit from adequate 25(OH)D for CRC prevention.

AB - Background: Higher circulating 25-hydroxyvitamin-D [25(OH)D] concentrations are consistently inversely associated with colorectal cancer (CRC) risk in observational studies. However, it is unknown whether this association depends on the functional GC-rs4588*A (Thr436Lys) variant encoding the vitamin D-binding protein-2 (DBP2) isoform, which may affect vitamin D status and bioavailability.Methods: We analyzed data from 1710 incident CRC cases and 1649 incidence-density-matched controls nested within three prospective cohorts of mostly Caucasians. Study-specific incidence rate ratios (RRs) for associations of prediagnostic, season-standardized 25(OH)D concentrations according to DBP2 isoform with CRC were estimated using multivariable unconditional logistic regression and were pooled using fixed-effects models. All statistical significance tests were two-sided.Results: The odds of having 25(OH)D concentrations less than 50 nmol/L (considered insufficient by the Institute of Medicine) were 43% higher for each DBP2-encoding variant (rs4588*A) inherited (per DBP2 odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.27 to 1.62, Ptrend = 1.2 × 10-8). The association of 25(OH)D concentrations with CRC risk differed by DBP2: 25(OH)D concentrations considered sufficient (≥ 50 nmol/L), relative to deficient (< 30 nmol/L), were associated with a 53% lower CRC risk among individuals with the DBP2 isoform (RR = 0.47, 95% CI = 0.33 to 0.67), but with a non-statistically significant 12% lower risk among individuals without it (RR = 0.88, 95% CI = 0.61 to 1.27) (Pheterogeneity = .01).Conclusions: Our results suggest that the 25(OH)D-CRC association may differ by DBP isoform, and those with a DBP2-encoding genotype linked to vitamin D insufficiency may particularly benefit from adequate 25(OH)D for CRC prevention.

U2 - 10.1093/jncics/pkz083

DO - 10.1093/jncics/pkz083

M3 - Article

C2 - 32337495

SN - 2515-5091

VL - 4

SP - pkz083

JO - JNCI Cancer Spectrum

JF - JNCI Cancer Spectrum

IS - 1

ER -

Association of Circulating Vitamin D With Colorectal Cancer Depends on Vitamin D-Binding Protein Isoforms: A Pooled, Nested, Case-Control Study

Abstract

Access to Document

Fingerprint

Cite this