Expression of vitamin D receptor and vitamin D status in patients with oral neoplasms and effect of vitamin D supplementation on quality of life in advanced cancer treatment

Akshay Anand, Suyash Singh, Abhinav A Sonkar, Nuzhat Husain, Kul Ranjan Singh, Sudhir Singh, Jitendra K Kushwaha, Akshay Anand, Suyash Singh, Abhinav A Sonkar, Nuzhat Husain, Kul Ranjan Singh, Sudhir Singh, Jitendra K Kushwaha

Abstract

Aim of the study: Vitamin D receptor (VDR) expression and serum vitamin D scores in oral premalignant lesions and oral cancer have not been widely analyzed. The role of vitamin D supplementation in advanced oral cancer for improving quality of life (QOL) is also a matter of research.

Material and methods: Vitamin D receptor expression and vitamin D scores were analyzed in normal oral mucosa (n = 95), leukoplakia (n = 23) and oral cancer (n = 87). 45 patients with advanced oral cancer subjected to chemoradiation were evaluated for the effect of vitamin D supplementation on most observable QOL parameters such as oral mucositis, swallowing performance and overall QOL.

Results: Vitamin D receptor expression was increased in oral neoplastic lesions. Vitamin D scores were significantly lower in cases compared to healthy controls (p = 0.002). Vitamin D supplementation significantly reduced the therapy-related toxicities in advanced cancer, thus reducing morbidity and improving QOL.

Conclusions: Vitamin D receptor expression is increased in premalignant lesions and oral cancer. Vitamin D insufficiency and deficiency are prevalent in patients with oral neoplastic lesions. Vitamin D supplementation has a role in reducing treatment-related toxicities, especially in advanced cancer.

Keywords: calcidiol levels; calcitriol receptor; oral neoplasms; quality of life.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Vitamin D receptor immunohistochemistry in A) Adjacent epithelium, B) Transition zone and C) Oral squamous cell carcinoma showing an increasing trend in the nuclear expression of vitamin D receptor from A to C (DAB × 200 × digital magnification)

References

    1. Sinha N, Mukhopadhyay S, Das DN, et al. Relevance of cancer initiating/stem cells in carcinogenesis and therapy resistance in oral cancer. Oral Oncol. 2013;49:854–62.
    1. Grimm M, Schmitt S, Teriete P, et al. A biomarker based detection and characterization of carcinomas exploiting two fundamental biophysical mechanisms in mammalian cells. BMC Cancer. 2013;13:569.
    1. Kornfehl J, Formanek M, Temmel A, Knerer B, Willheim M. Antiproliferative effects of the biologically active metabolite of vitamin D3 (1,25 [OH] 2 D3) on head and neck squamous cell carcinoma cell lines. Eur Arch Otorhinolaryngol. 1996;253:341–4.
    1. Satake K, Takagi E, Ishii A, et al. Anti-tumor effect of vitamin A and D on head and neck squamous cell carcinoma. Auris Nasus Larynx. 2003;30:403–12.
    1. Prudencio J, Akutsu N, Benlimame N, et al. Action of low calcemic 1alpha,25-dihydroxyvitamin D3 analogue EB1089 in head and neck squamous cell carcinoma. J Natl Cancer Inst. 2001;93:745–53.
    1. Meier JD, Enepekides DJ, Poirier B, Bradley CA, Albala JS, Farwell DG. Treatment with 1-alpha, 25-dihydroxyvitamin D3 (vitamin D3) to inhibit carcinogenesis in the hamster buccal pouch model. Arch Otolaryngol Head Neck Surg. 2007;133:1149–52.
    1. Osafi J, Hejazi A, Stutz DD, et al. Differential effects of 1,25-dihydroxyvitamin D (3) on oral squamous cell carcinomas in vitro. J Diet Suppl. 2014;11:145–54.
    1. Dalirsani Z, Farajnia S, Javadzadeh Y, et al. The effects of 5-fluorouracil alone and in combination with 13-cis retinoic acid and vitamin D3 on human oral squamous cell carcinoma lines. J Contemp Dent Pract. 2012;13:345–50.
    1. Dev R, Del Fabbro E, Schwartz GG, et al. Preliminary report: vitamin D deficiency in advanced cancer patients with symptoms of fatigue or anorexia. Oncologist. 2011;16:1637–41.
    1. Stone CA, Kenny RA, Healy M, et al. Vitamin D depletion: of clinical significance in advanced cancer? Support Care Cancer. 2011;19:865–7.
    1. Christakos S, Dhawan P, Verstuyf A, et al. Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects. Physiol Rev. 2016;96:365–408.
    1. Zehnder D, Bland R, Williams MC, et al. Extrarenal expression of 25- hydroxyvitamin d(3)-1 alpha-hydroxylase. J Clin Endocrinol Metab. 2001;86:888–94.
    1. Thorne J, Campbell MJ. The vitamin D receptor in cancer. Proc Nutr Soc. 2008;67:115–27.
    1. Remmele W, Stegner HE. Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Pathologe. 1987;8:138–40.
    1. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911–30.
    1. Garland CF, Garland FC, Gorham ED, et al. The role of vitamin D in cancer prevention. Am J Public Health. 2006;96:252–61.
    1. Schubert MM, Williams BE, Lloid ME, et al. Clinical assessment scale for the rating of oral mucosal changes associated with bone marrow transplantation development of an oral mucositis index. Cancer. 1992;69:2469–77.
    1. List MA, Siston A, Haraf D, Schumm P, Kies M, Stenson K, Vokes EE. Quality of life and performance in advanced head and neck cancer patients on concomitant chemoradiotherapy: A Prospective Examination. J Clin Oncol. 1999;17:1020–8.
    1. Feldman D, Krishnan AV, Swami S, et al. The role of vitamin D in reducing cancer risk and progression. Nat Rev Cancer. 2014;14:342–57.
    1. Holick M. The use and interpretation of assays for vitamin D and its metabolites. J Nutr. 1990;120:1464–9.
    1. Mitra D, Bell N. Racial, geographic, genetic and body habitus effects on vitamin D metabolism. In: Feldman D, Glorieux FH, Pike JW, editors. Vitamin D. San Diego, Calif: Academic Press; 1997. pp. 521–32.
    1. Agarwal KS, Mughal MZ, Upadhyay P, et al. The impact of atmospheric pollution on vitamin D status of infants and toddlers in Delhi, India. Arch Dis Child. 2002;87:111–3.
    1. Gupta R, Gupta A. Vitamin D Deficiency in India: Prevalence, Causalities and Interventions. Nutrients. 2014;6:729–75.
    1. Arem H, Weinstein SJ, Horst RL, et al. Serum 25-hydroxyvitamin D and risk of oropharynx and larynx cancers in Finnish men. Cancer Epidemiol Biomarkers Prev. 2011;20:1178–84.
    1. Yuan FN, Valiyaparambil J, Woods M, Tran H, Pant R, Adams JS, Mallya SM. Vitamin D signaling regulates oral keratinocyte proliferation in vitro and in vivo. Int J Oncol. 2014;44:1625–33.
    1. Orell-Kotikangas H, Schwab U, Osterlund P, et al. High prevalence of vitamin D insufficiency in patients with head and neck cancer at diagnosis. Head Neck. 2012;34:1450–5.
    1. Afzal S, Bojesen SE, Nordestgaard BG. Low plasma 25-hydroxyvitamin D and risk of tobacco-related cancer. Clin Chem. 2013;59:771–80.
    1. Wactawski-Wende J, Kotchen JM, Anderson GL, et al. Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med. 2006;354:684–96.
    1. Tangrea J, Helzlsouer K, Pietinen P, Taylor P, Hollis B, Virtamo J, Albanes D. Serum levels of vitamin D metabolites and the subsequent risk of colon and rectal cancer in Finnish men. Cancer Causes Control. 1997;8:615–25.
    1. Rossi M, McLaughlin JK, Lagiou P, et al. Vitamin D intake and breast cancer risk: a case-control study in Italy. Ann Oncol. 2009;20:374–8.
    1. Lefkowitz ES, Garland CF. Sunlight, vitamin D, and ovarian cancer mortality rates in US women. Int J Epidemiol. 1994;23:1133–6.
    1. Hanchette CL, Schwartz GG. Geographic patterns of prostate cancer mortality. Evidence for a protective effect of ultraviolet radiation. Cancer. 1992;70:2861–9.
    1. Lipworth L, Rossi M, McLaughlin JK, Negri E, Talamini R, Levi F, Franceschi S, La Vecchia C. Dietary vitamin D and cancers of the oral cavity and esophagus. Ann Oncol. 2009;20:1576–81.
    1. Visacri MB, Ferrari GB, Pimentel R, Ambrósio RD, Lima CS, Mazzola PG, Moriel P. Evaluation of the quality of life of patients before treatment of squamous cell carcinoma of the head and neck by means of chemoradiotherapy. Contemp Oncol (Pozn) 2015;19:148–53.
    1. Gao Y, Himizu M, Amada S, Ozaki Y, Aso T. The effects on vitamin of chemotherapy D metabolism including cisplatin. Endocr J. 1993;40:737–42.
    1. Fink M. Vitamin D deficiency is a cofactor of chemotherapy-induced mucocutaneous toxicity and dysgeusia. J Clin Oncol. 2011;29:e81–2.
    1. Kitchen D, Hughes B, Gill I, O’Brien M, Rumbles S, Ellis P, Harper P, Stebbing J, Rohatgi N. The relationship between vitamin D and chemotherapy-induced toxicity – a pilot study. Br J Cancer. 2012;107:158–60.
    1. Dobroś K, Hajto-Bryk J, Wróblewska M, Zarzecka J. Radiation-induced caries as the late effect of radiation therapy in the head and neck region. Contemp Oncol (Pozn) 2016;20:287–90.
    1. Delanian S, Balla-Mekias S, Lefaix JL. Striking regression of chronic radiotherapy damage in a clinical trial of combined pentoxifylline and tocopherol. J Clin Oncol. 1999;17:3283–90.
    1. Borek C. Antioxidants and radiation therapy. J Nutr. 2004;134:3207S–3209S.
    1. Block K, Koch A, Mead M, et al. Re: Should Supplemental Antioxidant Administration Be Avoided During Chemotherapy and Radiation Therapy? J Natl Cancer Inst. 2009;101:124–5. author reply 125-6.
    1. Brouckaert O, Paridaens R, Floris G, Rakha E, Osborne K, Neven P. A critical review why assessment of steroid hormone receptors in breast cancer should be quantitative. Ann Oncol. 2013;24:47–53.
    1. Grimm M, Cetindis M, Biegner T, Lehman M, Munz A, Teriete P, Reinert S. Serum vitamin D levels of patients with oral squamous cell carcinoma (OSCC) and expression of vitamin D receptor in oral precancerous lesions and OSCC. Med Oral Patol Oral Cir Bucal. 2015;20:e188–95.
    1. Delvin EE, Lopez V, Levy E, Menard D. Developmental expression of calcitriol receptors, 9-kilodalton calcium-binding protein, and calcidiol 24-hydroxylase in human intestine. Pediatr Res. 1996;40:664–70.
    1. Huerta S, Irwin RW, Heber D, Go VL, Koeffler HP, Uskokovic MR, Harris DM. 1alpha,25-(OH)(2)-D(3) and its synthetic analogue decrease tumor load in the Apc(min) mouse. Cancer Res. 2002;62:741–6.
    1. Eisman JA, Martin TJ, MacIntyre I, Moseley JM. 1,25-dihydroxyvitamin-D receptor in breast cancer cells. Lancet. 1979;2:1335–6.
    1. Colston KW, Berger U, Wilson P, et al. Mammary gland 1,25-dihydroxyvitamin D3 receptor content during pregnancy and lactation. Mol Cell Endocrinol. 1988;60:15–22.
    1. Miller GJ, Stapleton GE, Hedlund TE, Moffat KA. Vitamin D receptor expression, 24-hydroxylase activity, and inhibition of growth by 1alpha,25- dihydroxyvitamin D3 in seven human prostatic carcinoma cell lines. Clin Cancer Res. 1995;1:997–1003.
    1. Reichrath J, Rafi L, Müller SM, et al. Immunohistochemical analysis of 1,25-dihydroxyvitamin D3 receptor in cervical carcinoma. Histochem J. 1998;30:561–7.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다