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Association between low levels of 1,25-dihydroxyvitamin D and breast cancer risk

  • Esther C Janowsky (a1), Gayle E Lester (a2), Clarice R Weinberg (a3), Robert C Millikan (a1), Joellen M Schildkraut (a4), Peter A Garrett (a1) and Barbara S Hulka (a1)...
Abstract
AbstractObjective

To determine if blood levels of 25-hydroxyvitamin D (25-D) or its active metabolite, 1,25-dihydroxyvitamin D (1,25-D), are lower in women at the time of first diagnosis of breast cancer than in comparable women without breast cancer.

Design

This was a clinic-based case–control study with controls frequency-matched to cases on race, age, clinic and month of blood drawing.

Setting

University-based breast referral clinics.

Subjects

One hundred and fifty-six women with histologically documented adenocarcinoma of the breast and 184 breast clinic controls.

Results

There were significant mean differences in 1,25-D levels (pmol ml−1) between breast cancer cases and controls; white cases had lower 1,25-D levels than white controls (mean difference ± SE: −11.08 ± 0.76), and black cases had higher 1,25-D levels than black controls (mean difference ± SE: 4.54 ± 2.14), although the number of black women in the study was small. After adjustment for age, assay batch, month of blood draw, clinic and sample storage time, the odds ratio (95% confidence interval, CI) for lowest relative to highest quartile was 5.2 (95% CI 2.1, 12.8) for white cases and controls. The association in white women was stronger in women above the median age of 54 than in younger women, 4.7 (95% CI 2.1, 10.2) vs. 1.5 (95% CI 0.7, 3.0). There were no case–control differences in 25-D levels in either group.

Conclusions

These data are consistent with a protective effect of 1,25-D for breast cancer in white women.

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Corresponding author
*Corresponding author: Email esther_janowsky@unc.edu
References
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1DeLuca HF, Ostrem V. The relationship between the vitamin D system and cancer. Adv. Exp. Med. Biol. 1987; 206: 413–29.
2Reichel H, Koeffler HP, Norman AW. The role of the vitamin D endocrine system in health and disease. N. Engl. J. Med. 1989; 320: 980–91.
3Manoglas SC. Vitamin D and its relevance to cancer. AntiCancer Res. 1987; 7: 625–38.
4Studzinski GP, Moore DC. Sunlight—can it prevent as well as cause cancer? Cancer Res. 1995; 55: 4014–22.
5Gorham ED, Garland FC, Garland CF. Sunlight and breast cancer incidence in the USSR. Int. J. Epidemiol. 1990; 19: 820–4.
6Garland FC, Garland CF, Gorham ED, Young JF. Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation. Prev. Med. 1990; 19: 614–22.
7Blot WJ, Fraumeni JF, Stone BJ. Geographic patterns of breast cancer in the United States. J. Natl. Cancer Inst. 1977; 59: 1407–11.
8Simard A, Vobecky J, Vobecky JS. Vitamin D deficiency and cancer of the breast: an unprovocative ecological hypothesis. Can. J. Public Health 1991; 82: 300–3.
9Chouvet C, Vicard E, Devonec M, Saez S. 1,25-dihydroxyvitamin D3 inhibitory effect on the growth of two human breast cancer cell lines (MCF-7, BT-20). J. Steroid Biochem. 1986; 24: 373–6.
10Frappart L, Falette N, Lefebvre MF, Bremond A, Vauzelle JL, Saez S. In vitro studies of effects of 1,25-dihydroxyvitamin D3 on the morphology of human breast cancer cell line BT-20. Differentiation 1989; 40: 63–9.
11Welsh J. Induction of apoptosis in breast cancer cells in response to vitamin D and antiestrogens. Biochem. Cell Biol. 1994; 72: 537–47.
12James SY, Mackay AG, Colston KW. Vitamin D derivatives in combination with 9-cis retinoic acid promote active cell death in breast cancer cells. J. Mol. Endocrinol. 1995; 14: 391–4.
13Tsoukas CD, Provvedini DM, Manolagas SC. 1,25-dihydroxyvitamin D3: a novel immunoregulatory hormone. Science 1984; 224(4656): 1438–40.
14Reinhardt TA, Ramberg CF, Horst RL. Comparison of receptor binding, biological activity, and in vivo tracer kinetics for 1,25-dihydroxyvitamin D3, 1,25-dihydroxyvitamin D2, and its 24 epimer. Arch. Biochem. Biophys. 1989; 273: 6471.
15Nemere I, Yoshimoto Y, Norman AW. Calcium transport in perfused duodena from normal chicks: enhancement within fourteen minutes of exposure to 1,25-dihydroxyvitamin D3. Endocrinology 1984; 115: 1476–83.
16Krishnan AV, Feldman D. Stimulation of 1,25-dihydroxyvitamin D3 receptor gene expression in cultured cells by serum and growth factors. J. Bone Miner. Res. 1991; 6: 1099–107.
17Love RR, Mazess RB, Barden HS, et al. Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer. N. Engl. J. Med. 1992; 326: 852–6.
18Holick MF. The use and interpretation of assays for vitamin D and its metabolites. J. Nutr. 1990; 120: 1464–9.
19Mawer EB, Walls J, Howell A, Davies M, Ratcliffe WA, Bundred NJ. Serum 1,25-dihydroxyvitamin D may be related inversely to disease activity in breast cancer with bone metastases. J. Clin. Endocrinol. Metab. 1997; 82: 118–22.
20Elledge RM, Clark GM, Chamness GC, Osborne CK. Tumor biologic factors and breast cancer prognosis among white, Hispanic, and black women in the United States. J. Natl. Cancer Inst. 1994; 86: 705–12.
21Abrams SA, O'Brien KO, Liang LK, Stuff JE. Differences in calcium absorption and kinetics between black and white girls aged 5–16 years. J. Bone Miner. Res. 1995; 10: 829–33.
22Meier DE, Luckey MM, Wallenstein S, Clemens TL, Orwoll ES, Waslien CI. Calcium, vitamin D, and parathyroid hormone status in young white and black women: association with racial differences in bone mass. J. Clin. Endocrinol. Metab. 1991; 72: 703–10.
23M'Buyamba-Kabangu JR, Fagard R, Lijnen P, Bouillon R, Lissens W, Amery A. Calcium, vitamin D–endocrine system, and parathyroid hormone in black and white males. Calcif. Tissue Int. 1987; 41: 70–4.
24Reasner CA, Dunn JF, Fetchik DA, et al. Alteration of vitamin D metabolism in Mexican-Americans. J. Bone Miner. Res. 1990; 5: 1317.
25Bell NH, Greene A, Epstein S, Oexmann MJ, Shaw S, Shary J. Evidence for alteration of the vitamin D–endocrine system in blacks. J. Clin. Invest. 1985; 76: 470–3.
26Loomis F. Skin-pigment regulation of vitamin D biosynthesis in man. Science 1967; 157: 501–6.
27Hiatt RA, Krieger N, Lobaugh B, Drezner MK, Vogelman JH, Orentreich N. Prediagnostic serum vitamin D and breast cancer. J. Natl. Cancer Inst. 1998; 90: 461–3.
28Garrett PA, Hulka BS, Kim YL, Farber RA. HRAS proto-oncogene polymorphism and breast cancer. Cancer Epidemiol. Biomark. Prev. 1993; 2: 131–8.
29Hosmer DW, Lemeshow S. Applied Logistic Regression. New York: John Wiley & Sons, 1989.
30SAS Companion for the Microsoft Windows Environment, version 6. Cary, NC: SAS Institute Inc., 1993.
31Breslow NE, Day NE. Statistical Methods in Cancer Research, Vol. I. The Analysis of Case–Control Studies. Lyon: International Agency for Research on Cancer, 1980.
32Harris JR, Lippman ME, Veronesi U, Willet W. Breast cancer. N. Engl. J. Med. 1992; 327: 319–28.
33Bouillon RA, Auwerx JH, Lissens WD, Pelemens WK. Vitamin D status in the elderly: seasonal substrate deficiency causes 1,25-hydroxyvitamin cholecalciferol deficiency. Am. J. Clin. Nutr. 1987; 45: 755–63.
34Sherman SS, Hollis BW, Tobin JD. Vitamin D status and related parameters in a healthy population: the effects of age, sex, and season. J. Clin. Endocrinol. Metab. 1990; 71: 405–13.
35Cantatore FP, Carrozzo M, Magle DM, D'Amore M, Pipitone V. Serum 1,25(OH)2D in the elderly and osteoporotic subjects from southern Italy. In: Norman AW, Schafer K, Grigoleit H-G, Herrath DV, eds. Vitamin D: Molecular, Cellular and Clinical Endocrinology. Proceedings of the Seventh Workshop on Vitamin D. New York: Walter de Gruyter & Co., 1988; 897–8.
36Halloran BP, Portale AA, Lonergan ET, Morris RC Jr. Production and metabolic clearance of 1,25-dihydroxyvitamin D in men: effect of advancing age. J. Clin. Endocrinol. Metab. 1990; 70: 318–23.
37Tsai KS, Wahner HW, Offord KP, Melton LJ III, Kumar RRiggs BL. Effect of aging on vitamin D stores and bone density in women. Calcif. Tissue Int. 1987; 40: 241–3.
38Gloth FM III, Gundberg CM, Hollis BW, Haddad JG, Tobin JD. Vitamin D deficiency in homebound elderly persons. JAMA 1995; 274: 1683–6.
39Leaver DD, Trechsel U, Fleisch H. How is plasma 1,25(OH)2D3 concentration regulated by dietary calcium? In: Norman AW, Schafer K, Grigoleit H-G, Herrath DV, eds. Vitamin D: Molecular, Cellular and Clinical Endocrinology. Proceedings of the Seventh Workshop on Vitamin D. New York: Walter de Gruyter & Co., 1988; 662–3.
40Weiss NS, Liff JM. Accounting for the multicausal nature of disease in the design and analysis of epidemiologic studies. Am. J. Epidemiol. 1983; 117: 1418.
41Webb R, Pilbeam C, Hanafin N, Holick M. An evaluation of the relative contribution of exposure to sunlight and of diet to the circulating concentrations of 25-hydroxyvitamin D in an elderly nursing home population in Boston. Am. J. Clin. Nutr. 1990; 51: 1075–81.
42Tsai KS, Heath H III, Kumar R, Riggs BL. Impaired vitamin D metabolism with aging in women. J. Clin. Invest. 1984; 73: 1668–72.
43Colston KW, Berger U, Coombes RC. Possible role for vitamin D in controlling breast cell proliferation. Lancet 1989: 1: 188–91.
44Lieberman UA. Inborn errors in vitamin D metabolism—their contributions to the understanding of vitamin D metabolism. In: Norman AW, Schafer K, Grigoleit H-G, Herrath DV, eds. Vitamin D: Molecular, Cellular and Clinical Endocrinology. Proceedings of the Seventh Workshop on Vitamin D. New York: Walter de Gruyter & Co., 1988; 935–47.
45Taylor JA, Hirvonen A, Watson M, Pittman G, Mohler JL, Bell DA. Association of, prostate cancer with vitamin D receptor gene polymorphism. Cancer Res. 1996; 56: 4108–10.
46Ikekawa N. Structures and biological activities of vitamin D metabolites and their analog. Med. Res. Rev. 1987; 7: 333–66.
47Matsumoto T. Cell differentiation and vitamin D. Nippon Naibunpi Gakki Zasshi 1992; 68(5): 526–37.
48Mehta RG, Moriarty RM, Mehta RR, et al. Prevention of preneoplastic mammary lesion development by a novel vitamin D analogue, 1a-hydroxyvitamin D5. J. Natl. Cancer. Inst. 1997; 89: 212–18.
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