Association of 25-hydroxyvitamin D, Cyclooxygenase-2 and Prostaglandin E2 Serum Levels in Breast Cancer Patients

Theresia Ilyan, Dwi Retnoningrum, Meita Hendrianingtyas, Dian Widyaningrum, Banundari Rachmawati

Abstract


BACKGROUND: Serum levels of 25-hydroxyvitamin D (25(OH)D), prostaglandin E2 (PGE2), and cyclooxygenase 2 (COX2) expression differ between breast cancer stages. Since, previous studies showed mixed results, in this study, we aimed to analyze vitamin D levels related to breast cancer stages and serum levels of COX2 and PGE2 in Indonesia.

METHODS: This was a cross sectional study involving 75 breast cancer patients. Subjects were divided into 3 groups, namely operable early stage (K1), locally advanced stage (K2), and advanced stage (K3). Venous blood samples were taken from each subject, then were analyzed for the 25(OH)D, COX2, and PGE2 serum levels by enzyme-linked immunosorbent assay (ELISA) method.

RESULTS: There were significant differences in 25(OH)D among groups (p=0.012); between K1 and K2 (p=0.009) and between K1 and K3 (p=0.023). However, there was no significant difference in serum COX2 level (p=0.328). There were significant differences of PGE2 among groups (p=0.002); between K1 and K2 (p=0.036) and between K1 and K3 (p=0.001). Correlation test showed that there were differences between 25(OH)D serum levels and PGE2 serum level (r=0.306, p=0.008) and also between 25(OH)D serum level and breast cancer stage (r=-0.229; p=0.048).

CONCLUSION: There were differences in serum Vitamin D and PGE2 levels at various stages of breast cancer. Serum 25(OH)D levels had weak correlation with breast cancer stage and PGE2 serum level. Serum vitamin D level in advanced breast cancer were lower than early stage breast cancer and indicate a poor prognosis.

KEYWORDS: breast cancer, 25-hydroxyvitamin D, cyclooxygenase 2, prostaglandin E2


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References


Shah R, Rosso K, Nathanson DS. Pathogenesis, prevention, diagnosis and treatment of breast cancer. World J Clin Oncol. 2014; 5: 283-98, CrossRef.

Kementerian Kesehatan RI. Keputusan Menteri Kesehatan Republik Indonesia Nomor HK.01.07/MENKES/414/2018 tentang Pedoman Nasional Pelayanan Kedokteran Tata Taksana Kanker Payudara. Jakarta: Kementerian Kesehatan RI; 2018.

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68: 394-424, CrossRef.

Tsuprykov O, Chen X, Hocher CF, Skoblo R, Lianghong Yin, Hocher B. Why should we measure free 25(OH) vitamin D? J Steroid Biochem Mol Biol. 2018; 180: 87-104, CrossRef.

Feldman D, Krishnan AV, Swami S, Giovannucci E, Feldman BJ. The role of vitamin D in reducing cancer risk and progression. Nat Rev Cancer. 2014; 14: 342-57, CrossRef.

Martínez-Reza I, Díaz L, Barrera D, Segovia-Mendoza M, Pedraza-Sánchez S, Soca-Chafre G, et al. Calcitriol inhibits the proliferation of triple-negative breast cancer cells through a mechanism involving the proinflammatory cytokines IL-1β and TNF-α. J Immunol Res. 2019; 2019: 6384278, CrossRef.

Bauer SR, Hankinson SE, Bertone-Johnson ER, Ding EL. Plasma vitamin D levels, menopause, and risk of breast cancer: Dose-response meta-analysis of prospective studies. Medicine (Baltimore). 2013; 92: 123-31, CrossRef.

Hossain S, Beydoun MA, Beydoun HA, Chen X, Zonderman AB, Wood RJ. Vitamin D and breast cancer: A systematic review and meta-analysis of observational studies. Clin Nutr ESPEN. 2019; 30: 170-84, CrossRef.

Atoum M, Alzoughool F. Vitamin D and breast cancer: latest evidence and future steps. Breast Cancer Basic Clin Res. 2017; 11: 1178223417749816, CrossRef.

Hatse S, Lambrechts D, Verstuyf A, Smeets A, Brouwers B, Vandorpe T, et al. Vitamin D status at breast cancer diagnosis: Correlation with tumor characteristics, disease outcome, and genetic determinants of vitamin D insufficiency. Carcinogenesis. 2012; 33: 1319-26, CrossRef.

Thanasitthichai S, Chaiwerawattana A, Prasitthipayong A. Association of vitamin D level with clinicopathological features in breast cancer. Asian Pacific J Cancer Prev. 2015; 16: 4881-3, CrossRef.

Palmieri C, MacGregor T, Girgis S, Vigushin D. Serum 25‐hydroxyvitamin D levels in early and advanced breast cancer. J Clin Pathol. 2006; 59: 1334-6, CrossRef.

Imtiaz S, Raza S, Muhammad A, Siddiqui N, Loya A. Vitamin D deficiency in newly diagnosed breast cancer patients. Indian J Endocrinol Metab. 2012; 16: 409-13, CrossRef.

Damayanti AY, Indarto D, Wasita B, Ardyanto TD. Indeks massa tubuh, asupan vitamin D, dan serum 25-hydroxyvitamin D pada pasien kanker payudara. J Gizi Klin Indones. 2017; 14: 56-63, CrossRef.

Alexanian A, Sorokin A. Cyclooxygenase 2: Protein-protein interactions and posttranslational modifications. Physiol Genomics. 2017; 49: 667-81, CrossRef.

Cordes T, Hoellen F, Dittmer C, Salehin D, Kümmel S. Correlation of prostaglandin metabolizing enzymes and serum PGE 2 levels with vitamin D receptor and serum 25 (OH)2 D3 levels in breast and ovarian cancer. Anticancer Res. 2012; 358: 351-7, PMID.

Jana D, Sarkar DK, Ganguly S. Role of cyclooxygenase 2 ( COX-2 ) in prognosis of breast cancer. Indian J Surg Oncol. 2014; 5: 59-65, CrossRef.

Gomez I, Foudi N, Longrois D, Norel X. The role of prostaglandin E 2 in human vascular inflammation. Prostaglandins Leukot Essent Fat Acids. 2013; 89: 55-63, CrossRef.

Yuan L, Jiang R, Yang Y, Ding S, Deng H. 1,25-Dihydroxyvitamin D 3 inhibits growth of the breast cancer cell line MCF-7 and downregulates cytochrome P4501B1 through the COX-2 / PGE2 pathway. Oncol Rep. 2012; 28: 2131-7, CrossRef.

Liu W, Zhang L, Xu HJ, Li Y, Hu CM, Yang JY, et al. The anti-inflammatory effects of vitamin D in tumorigenesis. Int J Mol Sci. 2018; 19: 2736, CrossRef.

Jeon SM, Shin EA. Exploring vitamin D metabolism and function in cancer. Exp Mol Med. 2018; 50: 20, CrossRef.

Thill M, Hoellen F, Becker S, Dittmer C, Fischer D, Kümmel S, et al. Expression of prostaglandin- and vitamin D-metabolising enzymes in benign and malignant breast cells. Anticancer Res. 2012; 32: 367-72, PMID.

de Sousa Almeida-Filho B, De Luca Vespoli H, Pessoa EC, Machado M, Nahas-Neto J, Nahas EAP. Vitamin D deficiency is associated with poor breast cancer prognostic features in postmenopausal women. J Steroid Biochem Mol Biol. 2017; 174: 284-9, CrossRef.

Janbabai G, Shekarriz R, Hassanzadeh H, Aarabi M, Samaneh Borhani S. A survey on the relationship between serum 25-hydroxy vitamin D level and tumor characteristics in patients with breast cancer. Int J Hematol Stem Cell Res. 2016; 10: 30-6, PMID.

Sofi NY, Jain M, Kapil U, Seenu V, R L, Yadav CP, et al. Reproductive factors, nutritional status and serum 25(OH)D levels in women with breast cancer: A case control study. J Steroid Biochem Mol Biol. 2018; 175: 200-4, CrossRef.

Xu F, Li M, Zhang C, Cui J, Liu J, Li J. Clinicopathological and prognostic significance of COX-2 immunohistochemical expression in breast cancer : a meta- analysis. Oncotarget. 2017; 8: 6003-12, CrossRef.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology Breast Cancer. Pennsylvania: NCCN; 2019.

Shamsi U, Khan S, Azam I, Khan AH, Maqbool A, Hanif M, et al. A multicenter case control study of association of vitamin D with breast cancer among women in Karachi, Pakistan. PLoS One. 2020; 15: e0225402, CrossRef.

Estébanez N, Gómez-Acebo I, Palazuelos C, Llorca J, Dierssen-Sotos T. Vitamin D exposure and risk of breast cancer: a meta-analysis. Sci Rep. 2018; 8: 9039, CrossRef.

Krishnan AV, Feldman D. Mechanisms of the anti-cancer and anti-inflammatory actions of vitamin D. Annu Rev Pharmacol Toxicol. 2011; 51: 311-36, CrossRef.

Kochel TJ, Goloubeva OG, Fulton AM. Upregulation of cyclooxygenase-2/prostaglandin E2 (COX-2/PGE2) pathway member multiple drug resistance-associated protein 4 (MRP4) and downregulation of prostaglandin transporter (PGT) and 15-prostaglandin dehydrogenase (15-PGDH) in triple-negative breast. Breast Cancer Basic Clin Res. 2016; 10: 61-70, CrossRef.

Moris D, Kontos M, Spartalis E, Fentiman IS. The role of NSAIDs in breast cancer prevention and relapse: current evidence and future perspectives. Breast Care. 2016; 11: 339-44, CrossRef.

Howe LR. Inflammation and breast cancer. Cyclooxygenase/prostaglandin signaling and breast cancer. Breast Cancer Res. 2007; 9: 210, CrossRef.

Frasor J, Weaver AE, Pradhan M, Mehta K. Synergistic up-regulation of prostaglandin E synthase expression in breast cancer cells by 17β-estradiol and proinflammatory cytokines. Endocrinology. 2008; 149: 6272-9, CrossRef.




DOI: https://doi.org/10.18585/inabj.v13i4.1684

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