RESEARCH ARTICLE |
https://doi.org/10.5005/jp-journals-10028-1600 |
A Brief Report on the Prevalence of Vitamin D3 Deficiency in Children with Brain Tumors
1,4Department of Neurosurgery, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
2Department of Neurosurgery, Dr. Rajendra Prasad Government Medical College, Kangra, Himachal Pradesh, India
3Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India
Corresponding Author: Ashish Aggarwal, Department of Neurosurgery, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India, Phone: +91 1722756707, e-mail: aaggarwal_7@yahoo.com
Received on: 25 March 2022; Accepted on: 20 June 2022; Published on: 31 December 2022
ABSTRACT
Introduction: For both benign and malignant brain tumors, the outcome continues to remain dismal despite the progress made in the last half a century. The picture is gloomier in the pediatric age-group. As for any disease with limited survival and high morbidity, it is imperative to study the disease etiology to have meaningful interventions. Apart from genetics that cannot be modified, environmental and dietary factors play a role in oncogenesis, and these are potentially modifiable. A lesser-studied aspect is the role of micronutrients in the causation of brain tumors, especially in early childhood. We analyzed the association of vitamin D3 (Vit D3) in children with brain tumors.
Methods and materials: A prospective study of 50 children diagnosed with brain tumors in early childhood (<5 years old) was carried out. Vit D3 levels were measured in the blood samples of these patients and their mothers. A correlation was established between levels of Vit D3 and brain tumors.
Results: Around 26 children (52%) with pediatric brain tumors (PBTs) had Vit D3 deficiency. Of the 50 patients whose mothers were also analyzed, 22 (44%) mothers had Vit D3 deficiency. Interestingly, out of 26 children with Vit D3 deficiency, 17 were those whose mothers were also having hypovitaminosis D3. If the mother is deficient in Vit D3, the odds ratio for a child to be deficient in Vit D3 is 7.2
Conclusion: Large majority of children with brain tumors and their mothers were found to have a deficiency of Vit D3. Further large studies are required before any meaningful prevention strategy can be formulated.
How to cite this article: Singla N, Kumar M, Praneeth K, et al. A Brief Report on the Prevalence of Vitamin D3 Deficiency in Children with Brain Tumors. J Postgrad Med Edu Res 2022;56(4):171-173.
Source of support: Nil
Conflict of interest: None
Keywords: Brain tumors, Deficiency, Vitamin D.
INTRODUCTION
The availability of advanced diagnostics, better surgical techniques, and adjuvant therapy has definitely improved survival in PBT, but the overall scenario remains dismal. The future strategy has to focus on disease etiology and therapeutic interventions in relation to these. Various carcinogens have been described in the literature. These include radiation (ionizing and nonionizing), N-nitroso compounds, and viral infections (John Cunningham virus, cytomegalovirus, human immunodeficiency virus, simian virus 40, varicella zoster, and chicken pox).1-5 Since many micronutrients like Vit B9, Vit B12, and Vit D3 play an important role in deoxyribonucleic acid (DNA) metabolism; it is logical to conclude that insufficiency of these nutrients could potentially lead to DNA damage or incorrect methylation leading to tumorigenesis.4,6,7
There has been a recent interest in the role of Vit D3 in tumorigenesis. Various mechanisms, which may be Vit D receptors (VDR) dependent or independent, have been suggested. Vit D 3 seems to affect every stage of tumorigenesis from initiation to spread.8-12 However, the journey from lab to actual clinical benefit is still not fully established. Furthermore, elaborate studies which can conclusively comment on the role of such micronutrients in PBT are lacking.
Since a deficiency of micronutrients is a potentially correctable risk factor, an understanding of its role in PBT etiology could be of value in prevention strategies. We studied the levels of Vit D3 in children with brain tumors.
MATERIALS AND METHODS
A prospective observational study of children <5 years of age suffering from brain tumors was carried out. Patients suspected of having brain tumors on the basis of clinical diagnosis underwent contrast-enhanced magnetic resonance imaging of the brain to have a provisional diagnosis. After obtaining informed consent, these patients underwent surgery for tumor removal as per department protocol. The tumor specimen was subjected to histopathology, and a final diagnosis was established. Those with recurrent brain tumor or on nutritional supplements were excluded. Ethical approval was obtained from the institutional ethical committee. Consent for participation in the study was obtained from parents. Blood samples of children and their mothers were collected at admission. These samples were analyzed for serum levels of cholecalciferol (Vit D3) by using direct chemiluminescence acridinium ester technology in the ADVIA Centaur® Siemens machine.
The normal value in our laboratory is 11–43 ng/mL. A deficiency of vitamins was considered if the measured value was less than the lower limit. The results from children and mothers were analyzed with respect to brain tumors and the incidence of hypovitaminosis D3.
RESULTS
The study group included 50 children and their mothers. Age of the children ranged from 4 to 56 months (mean 32 months). There were 28 males and 22 females. The age of mothers ranged from 23 to 46 years (mean 29 years).
The range of brain tumors found was—medulloblastoma in 16 children, pilocytic astrocytoma in four, primitive neuroectodermal tumor in two, craniopharyngioma in six, brainstem glioma in six children, and other tumors in rest.
A total of 26 (out of 50) and 22 mothers (out of 50) had Vit D3 deficiency (Table 1).
| Maternal Vit D3 levels | |||||
|---|---|---|---|---|---|
| Hypovitaminosis | Normal | Hypervitaminosis | Total | ||
| Vit D3 levels in children | Hypovitaminosis | 17 | 6 | 3 | 26 |
| Normal | 4 | 13 | 0 | 17 | |
| Hypervitaminosis | 1 | 6 | 0 | 7 | |
| Total | 22 | 25 | 3 | 50 | |
Interestingly, we found that of the 26 children with VitD3 deficiency, 17 were the ones whose mothers also had hypovitaminosis D3. If the mothers were deficient in Vit D3, the odds ratio for a child to be having hypovitaminosis Vit D3 was 7.2.
DISCUSSION
Carcinogenesis is a complex multifactorial process. These factors include genetic and environmental or what is known as—“Nature or Nurture.” An individual cannot change his/her genetic makeup, and therefore, the genetic factors influencing carcinogenesis remain largely unmodifiable. Since environmental factors can potentially be tweaked to our advantage, a major thrust of cancer research is focused on these factors.
Children <5 years of age, in the growing phase, have a high nutrient demand. Nutrient deficiency during intrauterine life or in early childhood can potentially lead to faulty DNA production and hence predispose them to tumor formation.
The role of certain vitamins is paramount in DNA methylation, cell division, and differentiation. Deficiency of Vit B9, Vit B12, and Vit D3 plays a role in the development of certain childhood brain tumors like medulloblastoma, primitive neuroectodermal tumors, and glioma.6,13
In the present study, we found that majority (56%) of children with brain tumors had Vit D3 deficiency. Of these, 65% were the ones whose mothers also had Vit D3 deficiency. It appears feasible that during a crucial stage of organogenesis, in utero, when cells are rapidly dividing, micronutrient deficiency can lead to faulty DNA production leading to tumorigenesis.
Vitamin D3 (Vit D3) deficiency has been implicated in the causation of as many as 18 different types of cancers. Breast cancer exhibits antiproliferative effects through both VDR and independent pathways.10 In malignant pleural mesothelioma, calcitriol decreases cell viability and also decreases proliferation. It also augments the effect of chemotherapy.11
Various hypothesis has been suggested explaining the role of Vit D3 as an antitumorigenic agent during the initiation and progression of the tumor. During the initiation phase, Vit D3 exhibits anti-inflammatory properties by inhibiting prostaglandin production. Vit D3 has an antiproliferative effect that causes cell cycle inhibition at different levels by inducing cyclin-dependent kinase 1 (CDK1), CDK 2, and downregulation of CDK1, leading to arrest in the growth 2 (G2) phase.14 Vit D3 can suppress vascular endothelial growth factor expression leading to antiangiogenesis with consequent growth inhibitory effect on endothelial cells. It can induce p21 expression and G1 phase cell cycle arrest in a mutant p53, which is VDR dependent. In addition, it limits reactive oxygen species-induced cell damage. During the tumor progression stage, it exhibits antiproliferative and differentiation action and also induces apoptosis through a mitochondrial-dependent pathway by the release of cytochrome c and protein of the B-cell lymphoma 2 families. It can induce differentiation in cancer cells through repression of Wnt/β-catenin signaling. Further, Vit D3 induces autophagic cell death.8,9,12
Further, Vit D3 inhibits the signaling of the Hedgehog pathway.13 Hedgehog pathway is an essential developmental signaling pathway in maintaining tissue polarity and stem cell population.15 Hedgehog signaling pathway has been especially implicated in the causation of medulloblastoma. The mitogenic nature of the sonic hedgehog (Shh) ligand leads to massive granule neuron progenitors in the developing cerebellum. If the Shh pathway is constitutively activated, proliferation persists beyond the normal development period leading to medulloblastoma.16 Shh pathway stimulation promotes secretion of angiogenic factors such as activin A, angiogenin, angiopoietin 1, granulocyte-macrophage colony-stimulating factor, matrix metallometallopeptidase-9, and urokinase-type plasminogen activator.17
Since adequate levels of Vit D3 appear to be so important as an anticancer agent, it is imperative to have a look at the reasons for its deficiency. These include poor sunlight exposure due to fewer outdoor activities. Increasing urbanization with small dwelling units and lifestyle changes are potential reasons. Children, instead of playing outdoors, prefer to spend their free time in front of the television, computers, smartphones, etc. In addition, certain diseases like pneumonia/diarrhea/mucositis, etc., can cause loss of appetite leading consequently to poor oral intake of dietary Vit D3. Infants and very young children might inherit Vit D3 deficiency from their mothers. Maternal dietary modifications at the level of the community have the potential to not only prevent commonly associated benign diseases linked with vitamin D deficiency (rickets) but may also prevent dreaded diseases like brain tumors in future progeny.
Limitations of the study include (1) the small size of the study group, (2) the lack of a control group of age-matched children to establish the causal relation, and (3) vitamin levels were measured at diagnosis, which after the phase of pathogenesis. We suggest a high-volume, multicentric prospective population study with a focus on the antenatal and immediate postnatal periods.
CONCLUSION
Children with brain tumors had a high prevalence (52%) of Vit D3 deficiency. Amongst such children, 65% patients’ mothers were also deficit in Vit D3. However, further large-scale studies are needed before any meaningful preventive strategy can be formulated.
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