The role of serum 25-hydroxyvitamin D, ionized calcium and phosphorus in breast cancer females: A case-control study

  • Authors

    • Nadia Abd El Moneim
    • Taha Hewala Ass. Prof and the head of Radiation Sciences DepartmentMedical Research Institute - Alexandria University165 El-Horreya Avenue, El- HadraPOB: 21561, Alexandria, Egypt
    • Mona Rashad
    • Yousria El-Sayed
    • Nehal Abu-Samra
    • Medhat Anwar
  • Breast Cancer, Incidence, Diagnosis, Prognosis, 25-Hydroxyvitamin D, Ionized Calcium, Phosphorus, CA15.3.
  • Aim: To evaluate the diagnostic and prognostic value of serum 25- hydroxyvitamin D (25(OH) D), ionized calcium and phosphorus in comparison with serum CA15.3 as the most commonly used breast cancer marker.

    Participants and methods: This study was conducted on 45 breast cancer female patients with recently detected breast cancer before surgery and 45 apparently healthy female controls of matched age, menstrual and socioeconomic status as breast cancer patients group. Serum 25(OH) D, ionized calcium, phosphorus and CA15.3 were measured using ready-for-use commercially available kits.

    Results: Serum levels of 25(OH) D and ionized calcium in the breast cancer patients group were significantly lower than those of the control group, while serum levels of phosphorus and CA15.3 in breast cancer patients group were significantly higher than those of the control group. The area under the ROC curve for serum ionized calcium (81.7%) was significantly greater than that of 25(OH) D (75.3%), CA 15.3 (70.1%) and phosphorus (62.8%). The odd’s ratio of vitamin D was 0.0937 (95% CI=0.0311-0.2823), of ionized calcium was 0.0464 (95% CI=0.015-0.141) and of phosphorus was 2.6801(95% CI=1.1269- 6.3742) in breast cancer patients group. Serum phosphorus was significantly correlated with age and menopausal status of breast cancer patients.

    Conclusion: Our results suggest that serum ionized calcium and 25(OH) D were superior to serum CA15.3 and phosphorus for prediction of breast cancer. In addition, our results indicate that 25 (OH) D and calcium may decrease the risk for breast cancer incidence, while phosphorus may increase this risk. None of the assayed biomarkers has a prognostic role in breast cancer.

  • References

    1. [1] Azaiza F, Cohen M. Health beliefs and rates of breast cancer screening among Arab women. J Women's Health 2006; 15:520-30.

      [2] Shoma AM, Mohamed MH, NoumanN, MohamedA, Ibrahim MI, Tobar SS, et al. Body image disturbance and surgical decision making in Egyptian postmenopausal breast cancer patients. World J Surg Oncol 2009; 7:66-77.

      [3] Randi G, Edefonti V, Ferraroni M, La Vecchia C, Decarli A. Dietary patterns and the risk of colorectal cancer and adenomas. Nutr Rev 2010; 68:389-408.

      [4] Conrads KA, Yi M, Simpson KA, Lucas DA, Camalier CE, Yu LR, et al. A combined proteome and microarray investigation of inorganic phosphate-induced pre-osteoblast cells. Mol. cellul proteomics: MCP 2005; 4:1284-96.

      [5] Chang SH, Yu KN, Lee YS, An GH, Beck GR Jr, Colburn NH, et al. Elevated inorganic phosphate stimulates Akt-ERK1/2-Mnk1 signaling in human lung cells. Am J Respirat Cell Mol Biol 2006; 35:528- 39?

      [6] Camalier CE, Young MR, Bobe G, Perella CM, ColburnNH, Beck GR Jr. Elevated phosphate activates N-ras and promotes cell transformation and skin tumorigenesis. Cancer Prev Res (Phila) 2010; 3:359-70.

      [7] Jin H, Chang SH, Xu CX, Shin JY, Chung YS, Park SJ, et al. High dietary inorganic phosphate affects lung through altering protein translation, cell cycle, and angiogenesis in developing mice. Toxicol sciences: an official journal of the Society of Toxicology 2007; 100:215-23.

      [8] Holick MF. Too little vitamin D in premenopausal women: why should we care? Am J Clin Nutr 2002; 76:3–4?

      [9] Hansen CM, Binderup L, Hamberg KJ, Carlberg C. Vitamin D and cancer: effects of 1,25(OH)2D3 and its analogs on growth control and tumorigenesis. Front Biosci 2001; 6: 820–48.

      [10] Grant WB. An estimate of premature cancer mortality in the USbecause of inadequate doses of solar ultraviolet- B radiation. Cancer 2002; 94:1867–75.

      [11] Garland F, Garland C, Gorham E, Young J Jr. Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation. Prev Med 1990; 19: 614–22.

      [12] Nesby-O'Dell S, Scanlon KS, Cogswell ME, Gillespie C, Hollis B W, Looker AC, et al. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988–1994. Am J Clin Nutr 2002; 76:187–92?

      [13] Wang Q, Lee D, Sysounthone V, Chandraratna RA, Christakos S, Korah R, et al. 1, 25-dihydroxyvitamin D3 and retinoic acid analogues induce differentiation in breast cancer cells with function- and cell-specific additive effects. Breast Cancer Res Treat 2001; 67: 157–68.

      [14] Almquist M, Manjer J, Bondeson L, Bondeson A. Serum calcium and breast cancer risk: results from a prospective cohort study of 7,847 women. Cancer Causes Control 2007; 18: 595–602.

      [15] Almquist M, Bondeson A, Bondeson L, Malm J, Manjer J. Serum levels of vitamin D, PTH and calcium and breast cancer risk-a prospective nested case-control study. Int J Cancer 2010; 127: 2159–68.

      [16] Duffy MJ. CA 15-3 and related mucins as circulating markers in breast cancer. Ann Clin Biochem 1999; 36: 579-86.

      [17] KeyhaniM, Nasizadeh S, Dehghannejad A.SerumCA15-3 measurment in breast cancer patients before and after mastectomy. Arch Iranian Med 2005; 8: 263-6.

      [18] Haskell CM, Lowitz BB, Casciato AD. Breast cancer. In: Casciato AD and Lowitz BB (Eds). Manual of clinical oncology 2nd ed.Boston,Toronto: Little and Brown Company; 1985: pp 150-65.

      [19] Rintoul RF. Operations on the breast. In: Fagquharson's textbook of operative surgery. 7th ed Rintoul RF (ed) Churchill-Livingstone Inc. 1986: p 279.

      [20] AbeloffMD, Lichter AS, Niederhuber JE, pierce LJ,AzizDC. Breast In: Abeloff MD, Armitage JO,LichterAS, NiederhuberJE; eds. Clinical oncology. 4th ed. Churchil living stone inc. (pub). Chapter 73, 1995; pp1617-714.

      [21] Meyerhaff ME, Opdycke WN. Ion-selctive electrodes. Adv clinic chem1986; 25:1-41.

      [22] Altman DG, Gardner M. Diagnostic tests. In: Altman DG, Machin D, Trevor NB, (eds). Statistics with confidence 2nd ed. BMJ Books; 2000: pp 105-19.

      [23] Engel P, Fagherazzi G, Boutten A, Dupré T, Mesrine S, Boutron-Ruault MC, et al. Serum 25(OH) vitamin D and risk of breast cancer: a nested case-control study from the French E3N cohort. Cancer Epidemiol Biomarkers Prev 2010; 19:2341-50.

      [24] Rejnmark L, Tietze A, Vestergaard P, Buhl L, Lehbrink M, Heickendorff L, et al. Reduced prediagnostic 25-hydroxyvitamin D levels in women with breast cancer: a nested case-control study. Cancer Epidemiol Biomarkers Prev 2009; 18:2655-60.

      [25] Eliassen AH, Spiegelman D, Hollis BW, Horst RL, Willett WC , Hankinson SE. Plasma 25-hydroxyvitamin D and risk of breast cancer in the Nurses' Health Study II. Breast Cancer Res 2011; 13:1-7.

      [26] Crew KD, Gammon MD, Steck SE, Hershman DL, Cremers S, Dworakowski E, et al. Association between plasma 25 hydroxyvitamin D and breast cancer risk. Cancer Prev Res 2009; 2:598-604.

      [27] Colston KW, Hansen CM. Mechanisms implicated in the growth-regulatory effects of vitamin D in breast cancer. Endocr Relat Cancer 2001; 9:45–59.

      [28] Pendas-Franco N, Gonzalez-Sancho JM, Suarez Y, Aguilera O, Steinmeyer A, Gamallo C, et al. Vitamin D regulates the phenotype of human breast cancer cells. Differentiation 2007; 75:193–207.

      [29] RoyPG, Thompson AM. Cyclin D1 and breast cancer. The Breast 2006; 15: 718–27.

      [30] Wang Q, Lee D, Sysounthone V, Chandraratna RA, Christakos S, KorahR,et al. 1,25-dihydroxyvitamin D3 and retinoic acid analogues induce differentiation in breast cancer cells with function- and cell-specific additive effects. Breast Cancer Res Treat 2001; 67: 157–68.

      [31] Berx G, Van Roy F. The E-cadherin/catenin complex: an important gatekeeper in breast cancer tumorigenesis and malignant progression. Breast Cancer Res 2001; 3:289-93.

      [32] Rocker D, Ravid A, Liberman UA, et al. () 1, 25- Dihydroxyvitamin D3 potentiates the cytotoxic effect of TNF on human breast cancer cells. Mol Cell Endocrinol 1994; 106:157–62.

      [33] Brosseau CM, Pirianov G, Colston KW. Involvement of stress activated protein kinases (JNK and p38) in 1, 25 dihydroxyvitaminD3-induced breast cell death. Steroids 2010; 75: 1082–8.

      [34] Narvaez CJ, Welsh J. Role of mitochondria and caspases in vitamin D-mediated Apoptosis of MCF-7 breast cancer cells. J Biol Chem 2001; 276:9101–7.

      [35] Wactawski-Wende J, Kotchen JM, Anderson GL, Assaf AR, Brunner RL, O'Sullivan MJ, et al. Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med 2006; 354: 684–96.

      [36] Narvaez CJ, ZinserGM, Welsh JE. Functions of 1, 25-dihydroxyvitamin D3 in mammary gland: from normal development to breast cancer. Steroids 2001; 66: 301–8.

      [37] Mantovani A, Pierotti MA. Cancer and inflammation: a compel relationship. Cancer Lett 2008; 267:180–1.

      [38] Krishnan AV, Swami S, Peng L, Wang J, Moreno J, Feldman D. Tissue-selective regulation of aromatase expression by calcitriol: implications for breast cancer therapy. Endocrinol 2010; 15:32–42.

      [39] Chen S. Aromatase and breast cancer. Front Biosci 1998; 3:922–33.

      [40] Freedman DM, Looker AC, ChangSC, Graubard BI. Prospective study of serum vitamin D and cancer mortality in the United States. J Natl Cancer Inst 2007; 99:1594 – 602.

      [41] Tretli S, Schwartz G, Torjesen PA, Robsahm TE. Serum levels of 25-hydroxyvitamin D and survival in Norwegian patients with cancer of breast, colon, lung and lymphoma:a population-based study. Cancer Causes Control 2012; 23:363–70.

      [42] Sergeev IN. Vitamin D and cellular Ca2+ signaling in breast cancer. Anticancer Res 2012; 32: 299-302.

      [43] Sprague BL, Skinner HG, Tentham-Dietz A, Lee KE, Klein BE, Klein R. Serum calcium and breast cancer risk in a prospective cohort study. Ann Epidemiol 2010; 20:82-5.

      [44] Sergeev IN. Calcium signaling in cancer and vitamin D. J Steroid Biochem Mol Biol 2005; 9: 145–51.

      [45] Martin E, Miller M, Krebsbach L, Beal J, Schwartz G, Sahmoun A. Serum calcium levels are elevated among women with untreated postmenopausal breast cancer. Cancer Causes Control 2009; 21:251-7.

      [46] Brada M, Rowley M, Grant DJ, Ashley S, Powels TJ. Hypercalcemia in patients with disseminated breast cancer. Acta Oncologica 1990; 29:577-80.

      [47] Newmark HL, Lipkin M, Maheshwari N. Colonic hyperplasia and hyperproliferation induced by a nutritional stress diet with four components of Western-style diet. J National Cancer Institute 1990; 82:491–6.

      [48] Hers I, Vincent E, Tavare J.M. Akt signaling in health and disease. Cell Signal 2011; 23: 1515–27.

      [49] Xu CX, Jin H, Lim HT, Kim JE, Shin JY, Lee ES, et al. High dietary inorganic phosphate enhances cap-dependent protein translation, cell-cycle progression, and angiogenesis in the livers of young mice. Am J Physiol Gastrointest Liver Physiol. 2000; 295: 654–63.

      [50] MethnneyNM. Calcium imbalances. In: Fluid and electrolyte balance 5th ed. Jones & Bartlett Learning LLC. 2012: pp 91-109.

      [51] McKane WR, Khosla S, Burritt MF, Kao PC, Wilson DM, Ory SJ, et al. Mechanism of renal calcium conservation with estrogen replacement therapy in women in early postmenopause. J Clin Endocrinol Metab 1995; 80: 3458–64.

      [52] Hewala T, Abd El-Moneim N, Ebeid S, Anwar M. The clinical significance of serum soluble Fas and p53 in breast cancer patients: comparison with serum CA15.3. Path Oncol Res 2012; 18: 841-8.

      [53] Park BW, OH JW, Park SH, Kim KS, Kim JH, et al. PreoperativeCA15-3 and CEA serum levels as predictor for breast cancer outcomes. Annals of Oncol 2008; 19: 675–81.

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    Abd El Moneim, N., Hewala, T., Rashad, M., El-Sayed, Y., Abu-Samra, N., & Anwar, M. (2015). The role of serum 25-hydroxyvitamin D, ionized calcium and phosphorus in breast cancer females: A case-control study. International Journal of Basic and Applied Sciences, 4(2), 228-237.