Deri Maliniteleri ve D Vitamini
Özet
D vitamini, genel vücut sağlığının yanı sıra melanom, melanom dışı deri kanserleri ve mikozis fungoides gibi deri malinitelerinin etyolojisi ve seyrinde de kritik bir rol oynamaktadır. Temel kaynakları güneş maruziyeti ile diyet veya takviyeler olan bu vitamin, anti-proliferatif, anti-anjiyogenik, pro-apoptotik etkileri ve DNA onarım süreçlerini güçlendirmesiyle bilinir. Klinik çalışmalarda, tanı anındaki düşük serum D vitamini düzeylerinin melanomda kalınlık, ülserasyon, nüks ve kötü prognozla ilişkili olduğu saptanmıştır. Melanom dışı deri kanserlerinde ise D vitamini reseptör (VDR) polimorfizmlerinin risk artışıyla bağıntısı bulunmuş, kalsipotriol gibi topikal D vitamini türevlerinin immün mekanizmaları tetikleyerek skuamöz hücreli karsinom insidansını azalttığı gösterilmiştir. Kutanöz T hücreli lenfoma (mikozis fungoides) hastalarında da D vitamini eksikliğinin stafilokok kolonizasyonunu ve sepsis riskini artırabileceği suçlanmaktadır. Bununla birlikte, epidemiyolojik çalışmalarda yüksek serum düzeyleri ile keratinosit kanseri riski arasında karmaşık ve çelişkili sonuçlar elde edilmiştir; bu durumun UV radyasyonunun kafa karıştırıcı etkisinden kaynaklanabileceği düşünülmektedir. Güncel veriler ışığında, deri kanserli hastalarda D vitamini takviyesi IIb kanıt düzeyinde B dereceli bir öneri olup, korunmasız güneşe maruz kalmadan kaçınılarak vitamin düzeylerinin dengeli bir diyet ve uygun takviyelerle normal sınırlarda tutulması tavsiye edilmektedir.
Vitamin D plays a critical role in the etiology and course of dermatological diseases as well as skin malignancies, including melanoma, non-melanoma skin cancers, and mycosis fungoides. Synthesized mainly through sun exposure or obtained via diet and supplements, it exhibits anti-proliferative, anti-angiogenic, and pro-apoptotic properties, while also strengthening DNA repair processes. Clinical studies indicate that low serum vitamin D levels at the time of diagnosis are associated with increased tumor thickness, ulceration, recurrence, and poor prognosis in melanoma patients. In non-melanoma skin cancers, certain vitamin D receptor (VDR) polymorphisms are linked to elevated risks, whereas topical vitamin D derivatives like calcipotriol have been shown to reduce squamous cell carcinoma incidence by inducing epidermal antitumor immunity. Furthermore, vitamin D deficiency in mycosis fungoides patients is implicated in increasing Staphylococcus colonization and sepsis frequency by reducing antimicrobial peptides. However, epidemiological data regarding the relationship between high serum levels and keratinocyte cancers remain contradictory, likely due to the confounding effects of concurrent ultraviolet radiation exposure. In light of current evidence, vitamin D supplementation in skin malignancies carries a grade B recommendation with a level IIb evidence level, suggesting that optimal levels should be maintained through a balanced diet and safe supplementation rather than unprotected sun exposure.
Referanslar
Kechichian E, Ezzedine K. Vitamin D and the Skin: An Update for Dermatologists. Am J Clin Dermatol. 2018;19 :223-35.
Navarro-Triviño FJ, Arias-Santiago S, Gilaberte-Calzada Y. Vitamin D and the Skin: A Review for Dermatologists. Actas Dermosifiliogr (Engl Ed). 2019;110:262-72.
Mahamat-Saleh Y, Aune D, Schlesinger S. 25-Hydroxyvitamin D status, vitamin D intake, and skin cancer risk: a systematic review and dose-response meta-analysis of prospective studies. Sci Rep. 2020;10:13151.
Gandini S, Raimondi S, Gnagnarella P, et al. Vitamin D and skin cancer: a meta-analysis. Eur J Cancer. 2009;45:634-41.
Christakos S, Ajibade DV, Dhawan P, et al. Vitamin D: metabolism. Rheum Dis Clin North Am. 2012;38:1-11.
Colotta F, Jansson B, Bonelli F. Modulation of inflammatory and immune responses by vitamin D. J Autoimmun. 2017 ;85:78-97.
Danielsson C, Törmä H, Vahlquist A, et al. Positive and negative interaction of 1,25-dihydroxyvitamin D3 and the retinoid CD437 in the induction of human melanoma cell apoptosis. Int J Cancer. 1999;81:467-70.
Danielsson C, Fehsel K, Polly P, et al. Differential apoptotic response of human melanoma cells to 1 alpha,25-dihydroxyvitamin D3 and its analogues. Cell Death Differ. 1998 ;5:946-52.
Bikle DD, Gee E, Pillai S. Regulation of keratinocyte growth, differentiation, and vitamin D metabolism by analogs of 1,25-dihydroxyvitamin D. J Invest Dermatol. 1993;101:713-8.
Ellison TI, Smith MK, Gilliam AC, et al. Inactivation of the vitamin D receptor enhances susceptibility of murine skin to UV-induced tumorigenesis. J Invest Dermatol. 2008;128:2508-17.
Wong G, Gupta R, Dixon KM, et al. 1,25-Dihydroxyvitamin D and three low-calcemic analogs decrease UV-induced DNA damage via the rapid response pathway. J Steroid Biochem Mol Biol. 2004;89-90:567-70.
Bikle DD. The Vitamin D Receptor as Tumor Suppressor in Skin. Adv Exp Med Biol. 2020;1268:285-306.
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.
Leiter U, Eigentler T, Garbe C. Epidemiology of skin cancer. Adv Exp Med Biol. 2014;810:120-40.
Orlow I, Reiner AS, Thomas NE, et al. GEM Study Group. Vitamin D receptor polymorphisms and survival in patients with cutaneous melanoma: a population-based study. Carcinogenesis. 2016 ;37:30-8.
Lim A, Shayan R, Varigos G. High serum vitamin D level correlates with better prognostic indicators in primary melanoma: A pilot study. Australas J Dermatol. 2018;59:182-7.
Danielsson C, Törmä H, Vahlquist A, et al. Positive and negative interaction of 1,25-dihydroxyvitamin D3 and the retinoid CD437 in the induction of human melanoma cell apoptosis. Int J Cancer. 1999;81:467-70.
Orlow I, Shi Y, Kanetsky PA, et al. GEM Study Group. The interaction between vitamin D receptor polymorphisms and sun exposure around time of diagnosis influences melanoma survival. Pigment Cell Melanoma Res. 2018;31:287-96.
Yudoh K, Matsuno H, Kimura T. 1alpha,25-dihydroxyvitamin D3 inhibits in vitro invasiveness through the extracellular matrix and in vivo pulmonary metastasis of B16 mouse melanoma. J Lab Clin Med. 1999;133:120-8.
Newton-Bishop JA, Beswick S, Randerson-Moor J, et al. Serum 25-hydroxyvitamin D3 levels are associated with breslow thickness at presentation and survival from melanoma. J Clin Oncol. 2009;27:5439-44.
: Newton-Bishop JA, Davies JR, Latheef F, et al. 25-Hydroxyvitamin D2 /D3 levels and factors associated with systemic inflammation and melanoma survival in the Leeds Melanoma Cohort. Int J Cancer.2015;136:2890–9.
Nürnberg B, Gräber S, Gärtner B, et al. Reduced serum 25-hydroxyvitamin D levels in stage IV melanoma patients. Anticancer Res. 2009;29:3669-74.
Davies JR, Field S, Randerson-Moor J, et al. An inherited variant in the gene coding for vitamin D-binding protein and survival from cutaneous melanoma: a BioGenoMEL study. Pigment Cell Melanoma Res. 2014;27:234-43.
Field S, Davies J, Bishop DT, et al. Vitamin D and melanoma. Dermatoendocrinol. 2013;5:121-9.
Randerson-Moor JA, Taylor JC, Elliott F, et al. Vitamin D receptor gene polymorphisms, serum 25-hydroxyvitamin D levels, and melanoma: UK case-control comparisons and a meta-analysis of published VDR data. Eur J Cancer. 2009 ;45:3271-81
Luo L, Orlow I, Kanetsky PA, et al. GEM Study Group. No prognostic value added by vitamin D pathway SNPs to current prognostic system for melanoma survival. PLoS One. 2017 Mar 21;12:e0174234.
Millen AE, Tucker MA, Hartge P, et al. Diet and melanoma in a case–control study. Cancer Epidemiol Biomarkers Prev. 2004;13:1042–51.
Veierød MB, Thelle DS, Laake P. Diet and risk of cutaneous malignant melanoma: a prospective study of 50,757 Norwegian men and women. Int J Cancer. 1997;71:600–4.
Eide MJ, Johnson DA, Jacobsen GR, et al. Vitamin D and nonmelanoma skin cancer in a health maintenance organization cohort. Arch Dermatol. 2011;147:1379-84.
Albert B, Hahn H. Interaction of hedgehog and vitamin D signaling pathways in basal cell carcinomas. Adv Exp Med Biol. 2014;810:329-41.
Burns EM, Guroji P, Ahmad I, et al. Association of Vitamin D Receptor Polymorphisms With the Risk of Nonmelanoma Skin Cancer in Adults. JAMA Dermatol. 2017;153:983-9.
Caini S, Boniol M, Tosti G, et al. Vitamin D and melanoma and non-melanoma skin cancer risk and prognosis: a comprehensive review and meta-analysis. Eur J Cancer. 2014;50:2649-58.
Bijlsma MF, Spek CA, Zivkovic D, et al. Repression of smoothened by patched-dependent (pro-)vitamin D3 secretion. PLoS Biol. 2006;4:e232.
Eide MJ, Johnson DA, Jacobsen GR, et al. Vitamin D and nonmelanoma skin cancer in a health maintenance organization cohort. Arch Dermatol. 2011;147:1379-84.
Asgari MM, Tang J, Warton ME, et al. Association of prediagnostic serum vitamin D levels with the development of basal cell carcinoma. J Invest Dermatol. 2010;130:1438-43.
Tang JY, Parimi N, Wu A, et al; Osteoporotic Fractures in Men (MrOS) Study Group. Inverse association between serum 25(OH) vitamin D levels and non-melanoma skin cancer in elderly men. Cancer Causes Control. 2010;21:387-91.
Park SM, Li T, Wu S, et al. Vitamin D Intake and Risk of Skin Cancer in US Women and Men. PLoS One. 2016;11:e0160308.
Talpur R, Cox KM, Hu M, et al. Vitamin D deficiency in mycosis fungoides and Sézary syndrome patients is similar to other cancer patients. Clin Lymphoma Myeloma Leuk. 2014;14:518-24.
Rasheed H, Hegazy RA, Gawdat HI, et al. Serum Vitamin D and Vitamin D Receptor Gene Polymorphism in Mycosis Fungoides Patients: A Case Control Study. PLoS One. 2016;11:e0158014.
Liu PT, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;311:1770-3.
Talpur R, Bassett R, Duvic M. Prevalence and treatment of Staphylococcus aureus colonization in patients with mycosis fungoides and Sézary syndrome. Br J Dermatol. 2008 ;159:105-12.
Yang K, Fung TT, Nan H. An Epidemiological Review of Diet and Cutaneous Malignant Melanoma. Cancer Epidemiol Biomarkers Prev. 2018;27:1115-22.
Vinceti M, Malagoli C, Fiorentini C, et al. Inverse association between dietary vitamin D and risk of cutaneous melanoma in a northern Italy population. Nutr Cancer. 2011;63:506-13.
Millen AE, Tucker MA, Hartge P, et al. Diet and melanoma in a case-control study. Cancer Epidemiol Biomarkers Prev. 2004;13:1042-51.
Hunter DJ, Colditz GA, Stampfer MJ, et al. Diet and risk of basal cell carcinoma of the skin in a prospective cohort of women. Ann Epidemiol. 1992;2:231-9.
Vojdeman FJ, Madsen CM, Frederiksen K, et al. Vitamin D levels and cancer incidence in 217,244 individuals from primary health care in Denmark. Int J Cancer. 2019;145:338-46.
Cunningham TJ, Tabacchi M, Eliane JP, et al. Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy. J Clin Invest. 2017;127:106-16.
Li M, Hener P, Zhang Z, et al. Topical vitamin D3 and low-calcemic analogs induce thymic stromal lymphopoietin in mouse keratinocytes and trigger an atopic dermatitis. Proc Natl Acad Sci U S A. 2006;103:11736-41.
Demehri S, Turkoz A, Manivasagam S, et al. Elevated epidermal thymic stromal lymphopoietin levels establish an antitumor environment in the skin. Cancer Cell. 2012;22:494-505.
Di Piazza M, Nowell CS, Koch U, et al. Loss of cutaneous TSLP-dependent immune responses skews the balance of inflammation from tumor protective to tumor promoting. Cancer Cell. 2012;22:479-93.
Rosenberg AR, Tabacchi M, Ngo KH, et al. Skin cancer precursor immunotherapy for squamous cell carcinoma prevention. JCI Insight. 2019;4:e125476.
Pommergaard HC, Burcharth J, Rosenberg J, et al. Combination chemoprevention with diclofenac, calcipotriol and difluoromethylornithine inhibits development of non-melanoma skin cancer in mice. Anticancer Res. 2013;33:3033-9.
