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Erschienen in: Cancer Causes & Control 7/2014

01.07.2014 | Original paper

Plasma free 25-hydroxyvitamin D, vitamin D binding protein, and risk of breast cancer in the Nurses’ Health Study II

verfasst von: Jun Wang, A. Heather Eliassen, Donna Spiegelman, Walter C. Willett, Susan E. Hankinson

Erschienen in: Cancer Causes & Control | Ausgabe 7/2014

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Abstract

Purpose

Prior prospective studies, including our own, have evaluated total plasma 25-hydroxyvitamin D [25(OH)D] and breast cancer risk with inconsistent results. However, recent studies suggest that some vitamin D functions may be more relevant to the unbound (free) fraction of 25(OH)D. Vitamin D binding protein (DBP) influences the free 25(OH)D levels and thus possibly the biological activities of vitamin D.

Methods

We conducted a case–control study nested within the Nurses’ Health Study II to evaluate the association of plasma free 25(OH)D and DBP with breast cancer risk in predominantly premenopausal women. Plasma samples were assayed for 25(OH)D and DBP in 584 case–control pairs. Free 25(OH)D levels were calculated based on plasma levels of total 25(OH)D, DBP, and a constant value representing average albumin levels. Conditional logistic regression was used to estimate relative risks (RRs) and 95 % confidence intervals (CIs).

Results

We found no association between plasma calculated free 25(OH)D and risk of breast cancer overall (highest vs. lowest quartile RR 1.21, 95 % CI 0.83–1.77, trend test p value = 0.50). No association was observed for plasma DBP as well (highest vs. lowest quartile RR 0.95, 95 % CI 0.67–1.36, trend test p value = 0.96). Results were similar by tumor hormone receptor status. Neither the total nor the calculated free 25(OH)D and breast cancer association substantially varied by plasma DBP levels.

Conclusions

Our study does not support an important role of either calculated circulating free 25(OH)D or circulating DBP levels in breast cancer risk among predominantly premenopausal women.
Literatur
1.
Zurück zum Zitat Lopes N, Paredes J, Costa JL, Ylstra B, Schmitt F (2012) Vitamin D and the mammary gland: a review on its role in normal development and breast cancer. Breast Cancer Res 14:211PubMedCentralPubMedCrossRef Lopes N, Paredes J, Costa JL, Ylstra B, Schmitt F (2012) Vitamin D and the mammary gland: a review on its role in normal development and breast cancer. Breast Cancer Res 14:211PubMedCentralPubMedCrossRef
2.
Zurück zum Zitat Zinser G, Packman K, Welsh J (2002) Vitamin D(3) receptor ablation alters mammary gland morphogenesis. Development 129:3067–3076PubMed Zinser G, Packman K, Welsh J (2002) Vitamin D(3) receptor ablation alters mammary gland morphogenesis. Development 129:3067–3076PubMed
3.
Zurück zum Zitat Zerwekh JE (2008) Blood biomarkers of vitamin D status. Am J Clin Nutr 87:1087S–1091SPubMed Zerwekh JE (2008) Blood biomarkers of vitamin D status. Am J Clin Nutr 87:1087S–1091SPubMed
4.
Zurück zum Zitat Bertone-Johnson ER, Chen WY, Holick MF et al (2005) Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 14:1991–1997PubMedCrossRef Bertone-Johnson ER, Chen WY, Holick MF et al (2005) Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 14:1991–1997PubMedCrossRef
5.
Zurück zum Zitat Chlebowski RT, Johnson KC, Kooperberg C et al (2008) Calcium plus vitamin D supplementation and the risk of breast cancer. J Natl Cancer Inst 100:1581–1591PubMedCentralPubMedCrossRef Chlebowski RT, Johnson KC, Kooperberg C et al (2008) Calcium plus vitamin D supplementation and the risk of breast cancer. J Natl Cancer Inst 100:1581–1591PubMedCentralPubMedCrossRef
6.
Zurück zum Zitat Freedman DM, Chang SC, Falk RT et al (2008) Serum levels of vitamin D metabolites and breast cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol Biomarkers Prev 17:889–894PubMedCentralPubMedCrossRef Freedman DM, Chang SC, Falk RT et al (2008) Serum levels of vitamin D metabolites and breast cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol Biomarkers Prev 17:889–894PubMedCentralPubMedCrossRef
7.
Zurück zum Zitat McCullough ML, Stevens VL, Patel R et al (2009) Serum 25-hydroxyvitamin D concentrations and postmenopausal breast cancer risk: a nested case control study in the Cancer Prevention Study-II Nutrition Cohort. Breast Cancer Res 11:R64PubMedCentralPubMedCrossRef McCullough ML, Stevens VL, Patel R et al (2009) Serum 25-hydroxyvitamin D concentrations and postmenopausal breast cancer risk: a nested case control study in the Cancer Prevention Study-II Nutrition Cohort. Breast Cancer Res 11:R64PubMedCentralPubMedCrossRef
8.
Zurück zum Zitat Rejnmark L, Tietze A, Vestergaard P et al (2009) Reduced prediagnostic 25-hydroxyvitamin D levels in women with breast cancer: a nested case–control study. Cancer Epidemiol Biomarkers Prev 18:2655–2660PubMedCrossRef Rejnmark L, Tietze A, Vestergaard P et al (2009) Reduced prediagnostic 25-hydroxyvitamin D levels in women with breast cancer: a nested case–control study. Cancer Epidemiol Biomarkers Prev 18:2655–2660PubMedCrossRef
9.
Zurück zum Zitat Agborsangaya CB, Surcel HM, Toriola AT et al (2010) Serum 25-hydroxyvitamin D at pregnancy and risk of breast cancer in a prospective study. Eur J Cancer 46:467–470PubMedCrossRef Agborsangaya CB, Surcel HM, Toriola AT et al (2010) Serum 25-hydroxyvitamin D at pregnancy and risk of breast cancer in a prospective study. Eur J Cancer 46:467–470PubMedCrossRef
10.
Zurück zum Zitat Almquist M, Bondeson AG, Bondeson L, Malm J, Manjer J (2010) Serum levels of vitamin D, PTH and calcium and breast cancer risk—a prospective nested case–control study. Int J Cancer 127:2159–2168PubMedCrossRef Almquist M, Bondeson AG, Bondeson L, Malm J, Manjer J (2010) Serum levels of vitamin D, PTH and calcium and breast cancer risk—a prospective nested case–control study. Int J Cancer 127:2159–2168PubMedCrossRef
11.
Zurück zum Zitat Engel P, Fagherazzi G, Boutten A et al (2010) Serum 25(OH) vitamin D and risk of breast cancer: a nested case–control study from the French E3 N cohort. Cancer Epidemiol Biomarkers Prev 19:2341–2350PubMedCrossRef Engel P, Fagherazzi G, Boutten A et al (2010) Serum 25(OH) vitamin D and risk of breast cancer: a nested case–control study from the French E3 N cohort. Cancer Epidemiol Biomarkers Prev 19:2341–2350PubMedCrossRef
12.
Zurück zum Zitat Eliassen AH, Spiegelman D, Hollis BW, Horst RL, Willett WC, Hankinson SE (2011) Plasma 25-hydroxyvitamin D and risk of breast cancer in the Nurses’ Health Study II. Breast Cancer Res 13:R50PubMedCentralPubMedCrossRef Eliassen AH, Spiegelman D, Hollis BW, Horst RL, Willett WC, Hankinson SE (2011) Plasma 25-hydroxyvitamin D and risk of breast cancer in the Nurses’ Health Study II. Breast Cancer Res 13:R50PubMedCentralPubMedCrossRef
13.
Zurück zum Zitat Kuhn T, Kaaks R, Becker S et al (2013) Plasma 25-hydroxyvitamin D and the risk of breast cancer in the European prospective investigation into cancer and nutrition: a nested case–control study. Int J Cancer 133:1689–1700PubMedCrossRef Kuhn T, Kaaks R, Becker S et al (2013) Plasma 25-hydroxyvitamin D and the risk of breast cancer in the European prospective investigation into cancer and nutrition: a nested case–control study. Int J Cancer 133:1689–1700PubMedCrossRef
14.
Zurück zum Zitat Scarmo S, Afanasyeva Y, Lenner P et al (2013) Circulating levels of 25-hydroxyvitamin D and risk of breast cancer: a nested case–control study. Breast Cancer Res 15:R15PubMedCentralPubMedCrossRef Scarmo S, Afanasyeva Y, Lenner P et al (2013) Circulating levels of 25-hydroxyvitamin D and risk of breast cancer: a nested case–control study. Breast Cancer Res 15:R15PubMedCentralPubMedCrossRef
15.
Zurück zum Zitat Mohr SB, Gorham ED, Alcaraz JE et al (2013) Serum 25-hydroxyvitamin D and breast cancer in the military: a case–control study utilizing pre-diagnostic serum. Cancer Causes Control 24:495–504PubMedCrossRef Mohr SB, Gorham ED, Alcaraz JE et al (2013) Serum 25-hydroxyvitamin D and breast cancer in the military: a case–control study utilizing pre-diagnostic serum. Cancer Causes Control 24:495–504PubMedCrossRef
16.
Zurück zum Zitat Mendel CM (1989) The free hormone hypothesis: a physiologically based mathematical model. Endocr Rev 10:232–274PubMedCrossRef Mendel CM (1989) The free hormone hypothesis: a physiologically based mathematical model. Endocr Rev 10:232–274PubMedCrossRef
17.
Zurück zum Zitat Bikle DD, Siiteri PK, Ryzen E, Haddad JG (1985) Serum protein binding of 1,25-dihydroxyvitamin D: a reevaluation by direct measurement of free metabolite levels. J Clin Endocrinol Metab 61:969–975PubMedCrossRef Bikle DD, Siiteri PK, Ryzen E, Haddad JG (1985) Serum protein binding of 1,25-dihydroxyvitamin D: a reevaluation by direct measurement of free metabolite levels. J Clin Endocrinol Metab 61:969–975PubMedCrossRef
18.
Zurück zum Zitat Bikle DD, Gee E, Halloran B, Kowalski MA, Ryzen E, Haddad JG (1986) Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein. J Clin Endocrinol Metab 63:954–959PubMedCrossRef Bikle DD, Gee E, Halloran B, Kowalski MA, Ryzen E, Haddad JG (1986) Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein. J Clin Endocrinol Metab 63:954–959PubMedCrossRef
19.
Zurück zum Zitat Powe CE, Ricciardi C, Berg AH et al (2011) Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. J Bone Miner Res 26:1609–1616PubMedCentralPubMedCrossRef Powe CE, Ricciardi C, Berg AH et al (2011) Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. J Bone Miner Res 26:1609–1616PubMedCentralPubMedCrossRef
20.
Zurück zum Zitat Bhan I, Powe CE, Berg AH et al (2012) Bioavailable vitamin D is more tightly linked to mineral metabolism than total vitamin D in incident hemodialysis patients. Kidney Int 82:84–89PubMedCentralPubMedCrossRef Bhan I, Powe CE, Berg AH et al (2012) Bioavailable vitamin D is more tightly linked to mineral metabolism than total vitamin D in incident hemodialysis patients. Kidney Int 82:84–89PubMedCentralPubMedCrossRef
21.
Zurück zum Zitat White P, Cooke N (2000) The multifunctional properties and characteristics of vitamin D-binding protein. Trends Endocrinol Metab 11:320–327PubMedCrossRef White P, Cooke N (2000) The multifunctional properties and characteristics of vitamin D-binding protein. Trends Endocrinol Metab 11:320–327PubMedCrossRef
22.
Zurück zum Zitat Safadi FF, Thornton P, Magiera H et al (1999) Osteopathy and resistance to vitamin D toxicity in mice null for vitamin D binding protein. J Clin Invest 103:239–251PubMedCentralPubMedCrossRef Safadi FF, Thornton P, Magiera H et al (1999) Osteopathy and resistance to vitamin D toxicity in mice null for vitamin D binding protein. J Clin Invest 103:239–251PubMedCentralPubMedCrossRef
23.
Zurück zum Zitat Mondul AM, Weinstein SJ, Virtamo J, Albanes D (2012) Influence of vitamin D binding protein on the association between circulating vitamin D and risk of bladder cancer. Br J Cancer 107:1589–1594PubMedCentralPubMedCrossRef Mondul AM, Weinstein SJ, Virtamo J, Albanes D (2012) Influence of vitamin D binding protein on the association between circulating vitamin D and risk of bladder cancer. Br J Cancer 107:1589–1594PubMedCentralPubMedCrossRef
24.
Zurück zum Zitat Weinstein SJ, Stolzenberg-Solomon RZ, Kopp W, Rager H, Virtamo J, Albanes D (2012) Impact of circulating vitamin D binding protein levels on the association between 25-hydroxyvitamin D and pancreatic cancer risk: a nested case–control study. Cancer Res 72:1190–1198PubMedCentralPubMedCrossRef Weinstein SJ, Stolzenberg-Solomon RZ, Kopp W, Rager H, Virtamo J, Albanes D (2012) Impact of circulating vitamin D binding protein levels on the association between 25-hydroxyvitamin D and pancreatic cancer risk: a nested case–control study. Cancer Res 72:1190–1198PubMedCentralPubMedCrossRef
25.
Zurück zum Zitat Weinstein SJ, Mondul AM, Kopp W, Rager H, Virtamo J, Albanes D (2013) Circulating 25-hydroxyvitamin D, vitamin D-binding protein and risk of prostate cancer. Int J Cancer 132:2940–2947PubMedCrossRef Weinstein SJ, Mondul AM, Kopp W, Rager H, Virtamo J, Albanes D (2013) Circulating 25-hydroxyvitamin D, vitamin D-binding protein and risk of prostate cancer. Int J Cancer 132:2940–2947PubMedCrossRef
26.
Zurück zum Zitat Tworoger SS, Sluss P, Hankinson SE (2006) Association between plasma prolactin concentrations and risk of breast cancer among predominately premenopausal women. Cancer Res 66:2476–2482PubMedCrossRef Tworoger SS, Sluss P, Hankinson SE (2006) Association between plasma prolactin concentrations and risk of breast cancer among predominately premenopausal women. Cancer Res 66:2476–2482PubMedCrossRef
27.
Zurück zum Zitat Rosner B (1983) Percentage points for a generalized ESD many-outlier procedure. Technometrics 25:165–172CrossRef Rosner B (1983) Percentage points for a generalized ESD many-outlier procedure. Technometrics 25:165–172CrossRef
28.
Zurück zum Zitat Manolio TA, Burke GL, Psaty BM et al (1995) Black-white differences in subclinical cardiovascular disease among older adults: the Cardiovascular Health Study. CHS Collaborative Research Group. J Clin Epidemiol 48:1141–1152PubMedCrossRef Manolio TA, Burke GL, Psaty BM et al (1995) Black-white differences in subclinical cardiovascular disease among older adults: the Cardiovascular Health Study. CHS Collaborative Research Group. J Clin Epidemiol 48:1141–1152PubMedCrossRef
29.
Zurück zum Zitat Bouillon R, Van Assche FA, Van Baelen H, Heyns W, De Moor P (1981) Influence of the vitamin D-binding protein on the serum concentration of 1,25-dihydroxyvitamin D3. Significance of the free 1,25-dihydroxyvitamin D3 concentration. J Clin Invest 67:589–596PubMedCentralPubMedCrossRef Bouillon R, Van Assche FA, Van Baelen H, Heyns W, De Moor P (1981) Influence of the vitamin D-binding protein on the serum concentration of 1,25-dihydroxyvitamin D3. Significance of the free 1,25-dihydroxyvitamin D3 concentration. J Clin Invest 67:589–596PubMedCentralPubMedCrossRef
30.
Zurück zum Zitat Durrleman S, Simon R (1989) Flexible regression models with cubic splines. Stat Med 8:551–561PubMedCrossRef Durrleman S, Simon R (1989) Flexible regression models with cubic splines. Stat Med 8:551–561PubMedCrossRef
31.
Zurück zum Zitat Govindarajulu US, Spiegelman D, Thurston SW, Ganguli B, Eisen EA (2007) Comparing smoothing techniques in Cox models for exposure-response relationships. Stat Med 26:3735–3752PubMedCrossRef Govindarajulu US, Spiegelman D, Thurston SW, Ganguli B, Eisen EA (2007) Comparing smoothing techniques in Cox models for exposure-response relationships. Stat Med 26:3735–3752PubMedCrossRef
32.
Zurück zum Zitat Marshall RJ, Chisholm EM (1985) Hypothesis testing in the polychotomous logistic model with an application to detecting gastrointestinal cancer. Stat Med 4:337–344PubMedCrossRef Marshall RJ, Chisholm EM (1985) Hypothesis testing in the polychotomous logistic model with an application to detecting gastrointestinal cancer. Stat Med 4:337–344PubMedCrossRef
33.
Zurück zum Zitat Bauer SR, Hankinson SE, Bertone-Johnson ER, Ding EL (2013) Plasma vitamin D levels, menopause, and risk of breast cancer: dose–response meta-analysis of prospective studies. Medicine. 92:123–131PubMedCrossRef Bauer SR, Hankinson SE, Bertone-Johnson ER, Ding EL (2013) Plasma vitamin D levels, menopause, and risk of breast cancer: dose–response meta-analysis of prospective studies. Medicine. 92:123–131PubMedCrossRef
34.
Zurück zum Zitat Mondul AM, Weinstein SJ, Moy KA, Mannisto S, Albanes D (2013) Vitamin D binding protein, circulating vitamin D, and risk of renal cell carcinoma. Int J Cancer. doi:10.1002/ijc.28596 PubMed Mondul AM, Weinstein SJ, Moy KA, Mannisto S, Albanes D (2013) Vitamin D binding protein, circulating vitamin D, and risk of renal cell carcinoma. Int J Cancer. doi:10.​1002/​ijc.​28596 PubMed
35.
Zurück zum Zitat Mondul AM, Weinstein SJ, Horst RL, Purdue M, Albanes D (2012) Serum vitamin D and risk of bladder cancer in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening trial. Cancer Epidemiol Biomarkers Prev 21:1222–1225PubMedCentralPubMedCrossRef Mondul AM, Weinstein SJ, Horst RL, Purdue M, Albanes D (2012) Serum vitamin D and risk of bladder cancer in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening trial. Cancer Epidemiol Biomarkers Prev 21:1222–1225PubMedCentralPubMedCrossRef
36.
Zurück zum Zitat Gann PH, Ma J, Hennekens CH, Hollis BW, Haddad JG, Stampfer MJ (1996) Circulating vitamin D metabolites in relation to subsequent development of prostate cancer. Cancer Epidemiol Biomarkers Prev 5:121–126PubMed Gann PH, Ma J, Hennekens CH, Hollis BW, Haddad JG, Stampfer MJ (1996) Circulating vitamin D metabolites in relation to subsequent development of prostate cancer. Cancer Epidemiol Biomarkers Prev 5:121–126PubMed
37.
Zurück zum Zitat Corder EH, Friedman GD, Vogelman JH, Orentreich N (1995) Seasonal variation in vitamin D, vitamin D-binding protein, and dehydroepiandrosterone: risk of prostate cancer in black and white men. Cancer Epidemiol Biomarkers Prev 4:655–659PubMed Corder EH, Friedman GD, Vogelman JH, Orentreich N (1995) Seasonal variation in vitamin D, vitamin D-binding protein, and dehydroepiandrosterone: risk of prostate cancer in black and white men. Cancer Epidemiol Biomarkers Prev 4:655–659PubMed
38.
Zurück zum Zitat Willnow TE, Nykjaer A (2010) Cellular uptake of steroid carrier proteins–mechanisms and implications. Mol Cell Endocrinol 316:93–102PubMedCrossRef Willnow TE, Nykjaer A (2010) Cellular uptake of steroid carrier proteins–mechanisms and implications. Mol Cell Endocrinol 316:93–102PubMedCrossRef
39.
Zurück zum Zitat Rowling MJ, Kemmis CM, Taffany DA, Welsh J (2006) Megalin-mediated endocytosis of vitamin D binding protein correlates with 25-hydroxycholecalciferol actions in human mammary cells. J Nutr 136:2754–2759PubMedCentralPubMed Rowling MJ, Kemmis CM, Taffany DA, Welsh J (2006) Megalin-mediated endocytosis of vitamin D binding protein correlates with 25-hydroxycholecalciferol actions in human mammary cells. J Nutr 136:2754–2759PubMedCentralPubMed
40.
Zurück zum Zitat Chlon TM, Taffany DA, Welsh J, Rowling MJ (2008) Retinoids modulate expression of the endocytic partners megalin, cubilin, and disabled-2 and uptake of vitamin D-binding protein in human mammary cells. J Nutr 138:1323–1328PubMedCentralPubMed Chlon TM, Taffany DA, Welsh J, Rowling MJ (2008) Retinoids modulate expression of the endocytic partners megalin, cubilin, and disabled-2 and uptake of vitamin D-binding protein in human mammary cells. J Nutr 138:1323–1328PubMedCentralPubMed
41.
Zurück zum Zitat Kotsopoulos J, Tworoger SS, Campos H et al (2010) Reproducibility of plasma and urine biomarkers among premenopausal and postmenopausal women from the Nurses’ Health Studies. Cancer Epidemiol Biomarkers Prev 19:938–946PubMedCentralPubMedCrossRef Kotsopoulos J, Tworoger SS, Campos H et al (2010) Reproducibility of plasma and urine biomarkers among premenopausal and postmenopausal women from the Nurses’ Health Studies. Cancer Epidemiol Biomarkers Prev 19:938–946PubMedCentralPubMedCrossRef
Metadaten
Titel
Plasma free 25-hydroxyvitamin D, vitamin D binding protein, and risk of breast cancer in the Nurses’ Health Study II
verfasst von
Jun Wang
A. Heather Eliassen
Donna Spiegelman
Walter C. Willett
Susan E. Hankinson
Publikationsdatum
01.07.2014
Verlag
Springer International Publishing
Erschienen in
Cancer Causes & Control / Ausgabe 7/2014
Print ISSN: 0957-5243
Elektronische ISSN: 1573-7225
DOI
https://doi.org/10.1007/s10552-014-0383-5

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