Vitamin D receptor gene polymorphisms in pediatric patients with leukemia-lymphoma: Does it have an impact on malignancy?

Year 2022, , 270 - 274, 31.10.2022

Sinem Gulcan Kersın Ayse Gulnur Tokuc Ahmet Arman Baris Yılmaz

https://doi.org/10.5472/marumj.1191178

Abstract

Objective: Genetic variations have been identified in specific regions of the Vitamin D receptor (VDR) gene and many studies were
investigating whether these variations are associated with malignancy. Studies in the VDR on children are scarce. In this study, we
aimed to investigate the VDR gene polymorphisms in pediatric patients with the diagnosis of leukemia and lymphoma.
Patients and Methods: Of the 99 participants included in this cross-sectional study, 59 were control, 40 were patients. Fok-I, Bsm-I
and Taq-I polymorphism of the VDR gene were investigated in both groups.
Results: While no significant difference was found in the genotype distribution of the three polymorphisms between the patient and
control groups, significant results were obtained in Bsm-I and Taq-I allele frequencies (Odds ratio=0.489; CI95%=0.275-0.871 and
0.519; CI95%=0.280-0.964) (p<0.05).
Conclusions: In this study, we found that the frequency of allele “A” for Bsm-I and allele “C” for Taq-I was lower in the patient group.
Contrary to most publications in the literature, polymorphisms were not found to be risk factors in our study.

Keywords

Childhood cancers, Leukemia, Lymphoma, VDR, Polymorphism

References

• Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin 2021;71:7-33. doi: 10.3322/caac.21654.
• Pearce SH, Cheetham TD. Diagnosis and management of vitamin D deficiency. BMJ 2010;340:b5664. doi:10.1136/bmj. b5664
• Deeb KK, Trump DL, Johnson CS. Vitamin D signaling pathways in cancer: potential for anticancer therapeutics. Nat Rev Cancer 2007; 7:684-700. doi:10.1038/nrc2196
• Köstner K, Denzer N, Muller CSL, Klein R, Tilgen W, Reichranth J. The Relevance of Vitamin D Receptor (VDR) gene polymorphisms for cancer: A review of the literature. Anticancer Res 2009; 29:3511-36. PMID: 19667145.
• Raimondi S, Harriet Johansson H, Patrick Maisonneuve P, Gandini S. Review and meta-analysis on vitamin D receptor polymorphisms and cancer risk. Carcinogenesis 2009; 30:1170-80. doi: 10.1093/carcin/bgp103.
• Thorne J, Campbell MJ. The vitamin D receptor in cancer. Proc Nutr Soc 2008; 67:15-22. doi: 10.1017/S002.966.5108006964.
• Beysel S, Eyerci N, Pinarli FA, et al. VDR gene FokI polymorphism as a poor prognostic factor for papillary thyroid cancer. Tumour Biol 2018; 40:101.042.8318811766. doi: 10.1177/101.042.8318811766.
• Yu ZH, Chen M, Zhang QQ, Hu X. The association of vitamin D receptor gene polymorphism with lung cancer risk: An update meta-analysis. Comb Chem High Throughput Screen 2018; 21:704-10. doi: 10.2174/138.620.7322666.190.12515055 7.
• Oh JY, Barrett-Connor E. Association between vitamin D receptor polymorphism and type 2 diabetes or metabolic syndrome in community-dwelling older adults: The Rancho Bernardo Study. Metabolism 2002; 51:356–9. doi: 10.1053/ meta.2002.29969.
• Rasool S, Kadla SA, Rasool V, et al. Role of the VDR Bsm1 and Apa1 polymorphisms in the risk of colorectal cancer in Kashmir. Oncol Res Treat 2014; 37:345-9. doi: 10.1159/000362859.
• Bretherton-Watt D, Given-Wilson R, Mansi JL, Thomas V, Carter N, Colston KW. Vitamin D receptor gene polymorphisms are associated with breast cancer risk in a UK Caucasian population. Br J Cancer 2001; 85:171-5. doi: 10.1054/bjoc.2001.1864.
• Guy M, Lowe LC, Bretherton-Watt D, Mansi JL, Colston KW. Approaches to evaluating the association of vitamin D receptor gene polymorphisms with breast cancer risk. Recent Results Cancer Res 2003; 164:43-54. doi: 10.1007/978-3-642- 55580-0_3.
• Zhang K, Song L. Association between vitamin D receptor gene polymorphisms and breast cancer risk: a meta-analysis of 39 studies. PLoS One 2014; 9:e96125. doi: 10.1371/journal. pone.0096125.
• Luo S, Guo L, Li Y, Wang S. Vitamin D receptor gene ApaI polymorphism and breast cancer susceptibility: a metaanalysis. Tumour Biol 2014; 35:785-90. doi: 10.1007/ s13277.013.1107-2.
• Tang C, Chen N, Wu M, Yuan H, Du Y. Fok1 polymorphism of vitamin D receptor gene contributes to breast cancer susceptibility: a meta-analysis. Breast Cancer Res Treat 2009; 117:391-9. doi: 10.1007/s10549.008.0262-4.
• Yang B, Liu S, Yang X, et al. Current evidence on the four polymorphisms of VDR and breast cancer risk in Caucasian women. MetaGene 2014; 2:41-9. doi: 10.1016/j. mgene.2013.09.008.
• Ruza E, Sotillo E, Sierrasesúmaga L, Azcona C, Patiño-García A. Analysis of polymorphisms of the vitamin D receptor, estrogen receptor, and collagen I genes and their relationship with height in children with bone cancer. J Pediatr Hematol Oncol 2003; 25:780-6. doi: 10.1097/00043.426.200310000- 00007.
• Yilmaz B, Tokuc AG, Koc A, Yesil E. Investigation of vitamin D receptor gene polymorphism in pediatric patients with brain cancer. Indian J Med Paediatr Oncol 2017; 38:128-32. doi: 10.4103/ijmpo.ijmpo_22_16.
• Purdue MP, Lan Q, Kricker A, Vajdic CM, Rothman N, Armstrong BK. Vitamin D receptor gene polymorphisms and risk of non-Hodgkin’s lymphoma. Haematologica 2007; 92:1145-6. doi: 10.3324/haematol.11053.
• Tekgündüz SA, Yeşil Ş, Ören AC, et al. Vitamin D receptor (VDR) polymorphisms in pediatric patients presenting with Hodgkin’s lymphoma. J Pediatr Hematol Oncol 2017; 39:e59-e61. doi: 10.1097/MPH.000.000.0000000664.
• Bienertová-Vašků J, Drábová K, Zlámal F, et al. Pre-treatment VD levels and VDR receptors as potential predictors of occurrence and overall survival in paediatric patients with solid tumours-a single institution pilot study. Tumour Biol 2016; 37: 9209-19. doi: 10.1007/s13277.016.4820-9.