Association between Vitamin D Receptor Polymorphism and Susceptibility to Oral Lichen Planus and Oral Squamous Cell Carcinoma

Document Type : Original

Authors

1 Oral and Maxillofacial Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

2 Dental Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

3 Clinical Research Development Unit, Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

4 School of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran.

5 Department of Oral and Maxillofacial Pathology, School of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran.

10.22038/ijorl.2024.73925.3489

Abstract

Introduction: Oral squamous cell carcinomas (OSCC) comprise 90-95% of oral cancers. Early diagnosis improved the survival rate of OSCC patients to 80–90%. Oral lichen planus (OLP) is a chorionic inflammatory disease with malignancy potential. The vitamin D receptor (VDR) plays a critical role in the pathogenesis of oral cancer. This study aimed to determine the association between VDR rs7975232 (Apa I) polymorphism and potential susceptibility to OLP and OSCC risks. Materials and Methods: In this prospective case-control study, a total of 120 blood samples were obtained from OSCC patients (n=29), OLP (n=50), and controls (n=40). VDR rs7975232 polymorphism was studied using the Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) method. Statistical analysis was performed with SPSS Version 23 software. Data were expressed as means ± standard deviation (SD). Age, sex, allelic frequency, and genotyping were compared using the chi-square test. A p-value of less than 0.05 was regarded as statistically significant. The disease risk was estimated by Odds ratio (OR) with a 95% confidence interval. Results: A significant age difference was observed between the controls and the OSCC group (p=0.001). A significant difference was observed in Aa and aa genotypes compared with AA between OSCCs and controls. Moreover, dominant (p<0.001), additive (p<0.001), and allelic (p=0.001) models were different between groups. Conclusion: There was a positive association between rs7975232 VDR polymorphism and susceptibility to OSCC. More experimental evidence must reveal the possible association between rs7975232 and the risk of OLP in a larger cohort.

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Main Subjects


1. Cakir OO, Yilmaz A, Demir E, Incekara K, Kose MO, Ersoy N. Association of the BsmI, ApaI, TaqI, Tru9I and FokI Polymorphisms of the Vitamin D Receptor Gene with Nephrolithiasis in the Turkish Population. Urology journal 2016; 13(1): 2509-18. 2. Wang S, Yang M, Li R, Bai J. Current advances in noninvasive methods for the diagnosis of oral squamous cell carcinoma: a review. European journal of medical research 2023; 28(1): 53. 3. Chai AWY, Lim KP, Cheong SC. Translational genomics and recent advances in oral squamous cell carcinoma. Seminars in cancer biology 2020; 61: 71-83. 4. Britannica TEoEsnpEB, 20 Mar. 2023, https:// www.britannica. com/ science/ single- nucleotide-polymorphism. Accessed 11 April 2023. 5. Alhetheli G, Al-Dhubaibi MS, Bahaj SS, AbdElneam AI. Vitamin D Receptor Gene Polymorphism ApaI as a Predisposing Factor for Psoriasis and Its Relation With Serum Vitamin D Levels and Psoriasis Severity. Cureus 2022; 14(12): e32715. 6. Usategui-Martín R, De Luis-Román DA, Fernández-Gómez JM, Ruiz-Mambrilla M, Pérez-Castrillón JL. Vitamin D Receptor (VDR) Gene Polymorphisms Modify the Response to Vitamin D Supplementation: A Systematic Review and Meta-Analysis. Nutrients 2022; 14(2). 7. Hama T, Norizoe C, Suga H, Mimura T, Kato T, Moriyama H, et al. Prognostic significance of vitamin D receptor polymorphisms in head and neck squamous cell carcinoma. PloS one 2011; 6(12): e29634. 8. Fathi N, Ahmadian E, Shahi S, Roshangar L, Khan H, Kouhsoltani M, et al. Role of vitamin D and vitamin D receptor (VDR) in oral cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2019; 109: 391-401. 9. Hamour AF, Klieb H, Eskander A. Oral lichen planus. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 2020; 192(31): E892. 10. Albu C-C, Bencze M-A, Dragomirescu A-O, Vlădan C, Albu Ş-D, Russu E-A, et al. Oral Lichen Planus Genetics Update. European Journal of Dental and Oral Health 2022; 3(4): 1-5. 11. Motahari P, Pournaghi Azar F, Rasi A. Role of Vitamin D and Vitamin D Receptor in Oral Lichen Planus: A Systematic Review. Ethiopian journal of health sciences 2020; 30(4): 615-22. 12. Jin T, Guo Y, Huang Z, Zhang Q, Huang Z, Zhang Y, et al. Vitamin D inhibits the proliferation of Oral Squamous Cell Carcinoma by suppressing lncRNA LUCAT1 through the MAPK pathway. Journal of Cancer 2020; 11(20): 5971-81. 13. Becker AL, Carpenter EL, Slominski AT, Indra AK. The Role of the Vitamin D Receptor in the Pathogenesis, Prognosis, and Treatment of Cutaneous Melanoma. Frontiers in oncology 2021; 11: 743667. 14. Dutta D, Sharma M, Aggarwal S, Mohindra R, Bhattacharya S, Kalra S. Vitamin D, Thyroid Autoimmunity and Cancer: An Interplay of Different Factors. Indian journal of endocrinology and metabolism 2019; 23(5): 507-13. 15. Shen H, Liu Q, Huang P, Fan H, Zang F, Liu M, et al. Vitamin D receptor genetic polymorphisms are associated with oral lichen planus susceptibility in a Chinese Han population. BMC oral health 2020; 20(1): 26. 16. Nigam K, Singh N, Yadav SK, Sanyal S. The Taq 1 polymorphism of Vitamin D receptor gene is associated with oral cancer and preoral cancer in North Indian population. Journal of cancer research and therapeutics 2023; 19(2): 403-7. 17. Laczmanski L, Laczmanska I, Lwow F. Association of select vitamin D receptor gene polymorphisms with the risk of tobacco-related cancers - a meta-analysis. Scientific reports 2019; 9(1): 16026. 18. Gnagnarella P, Raimondi S, Aristarco V, Johansson HA, Bellerba F, Corso F, et al. Vitamin D Receptor Polymorphisms and Cancer. Advances in experimental medicine and biology 2020; 1268: 53-114. 19. Rao J, Wu X, Zhou X, Deng R, Ma Y. Vitamin D receptor FOK I polymorphism and risk of hepatocellular carcinoma in HBV-infected patients. Hepatitis Monthly 2019; 19(1). 20. Serrano D, Gnagnarella P, Raimondi S, Gandini S. Meta-analysis on vitamin D receptor and cancer risk: focus on the role of TaqI, ApaI, and Cdx2 polymorphisms. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) 2016; 25(1): 85-96. 21. Hoan NX, Khuyen N, Giang DP, Binh MT, Toan NL, Anh DT, et al. Vitamin D receptor ApaI polymorphism associated with progression of liver disease in Vietnamese patients chronically infected with hepatitis B virus. BMC medical genetics 2019; 20(1): 201. 22. Mohammed AA, El-Matty DMA, Abdel-Azeem R, Raafat K, Hussein MA, El-Ansary AR, et al. Allelic Discrimination of Vitamin D Receptor Polymorphisms and Risk of Type 2 Diabetes Mellitus: A Case-Controlled Study. Healthcare (Basel, Switzerland) 2023; 11(4). 23. Kazemi SM, Esmaieli-Bandboni A, Veisi Malekshahi Z, Shahbaz Sardood M, Hashemi M, Majidzadeh K, et al. Vitamin D receptor gene polymorphisms and risk of breast cancer in Iranian women. Annals of medicine and surgery (2012) 2022; 73: 103150. 24. Matini AH, Jafarian-Dehkordi N, Bahmani B, Sharifi M, Jahantigh D, Mazoochi T. Association of ApaI and TaqI polymorphisms in VDR Gene with Breast Cancer. Asian Pacific journal of cancer prevention : APJCP 2020; 21(9): 2667-72. 25. Hoseinkhani Z, Rastegari-Pouyani M, Tajemiri F, Yari K, Mansouri K. Association of Vitamin D Receptor Polymorphisms (FokI (Rs2228570), ApaI (Rs7975232), BsmI (Rs1544410), and TaqI (Rs731236)) with Gastric Cancer in a Kurdish Population from West of Iran. Reports of biochemistry & molecular biology 2021; 9(4): 435-41. 26. Ramezani M, Mazani M, Tabatabaei M, Rahimian A, Mosaferi E, Hedayati M. Medullary thyroid cancer is associated with high serum vitamin D level and polymorphism of vitamin D receptors. Physiology international 2020; 107(1): 120-33. 27. Moossavi M, Parsamanesh N, Mohammadoo-Khorasani M, Moosavi M, Tavakkoli T, Fakharian T, et al. Positive correlation between vitamin D receptor gene FokI polymorphism and colorectal cancer susceptibility in South-Khorasan of Iran. Journal of cellular biochemistry 2018; 119(10): 8190-4. 28. Mahmoudi H, Keramat F, Saidijam M, Mohammadi Y, Khodavirdipour A, Alikhani MY. Polymorphisms in vitamin D receptor genes and its relation with susceptibility to brucellosis: a case-control study. Molecular biology reports 2023; 50(3): 2077-83. 29. Abdollahzadeh R, Moradi Pordanjani P, Rahmani F, Mashayekhi F, Azarnezhad A, Mansoori Y. Association of VDR gene polymorphisms with risk of relapsing-remitting multiple sclerosis in an Iranian Kurdish population. The International journal of neuroscience 2018; 128(6): 505-11. 30. Akhlaghi B, Firouzabadi N, Foroughinia F, Nikparvar M, Dehghani P. Impact of vitamin D receptor gene polymorphisms (TaqI and BsmI) on the incidence and severity of coronary artery disease: a report from southern Iran. BMC cardiovascular disorders 2023; 23(1): 113. 31. Mohammadnejad Z, Ghanbari M, Ganjali R, Afshari JT, Heydarpour M, Taghavi SM, et al. Association between vitamin D receptor gene polymorphisms and type 1 diabetes mellitus in Iranian population. Molecular biology reports 2012; 39(2): 831-7. 32. Naderi N, Farnood A, Habibi M, Derakhshan F, Balaii H, Motahari Z, et al. Association of vitamin D receptor gene polymorphisms in Iranian patients with inflammatory bowel disease. Journal of gastroenterology and hepatology 2008; 23(12): 1816-22. 33. Grimm M, Shokri B, Alexander D, Munz A, Hoffmann J, Reinert S. Is 1,25-dihydroxyvitamin D3 receptor expression a potential Achilles' heel of CD44+ oral squamous cell carcinoma cells? Targeted oncology 2013; 8(3): 189-201. 34. Nigam K, Gupta S, Singh N, Yadav SK, Sanyal S. XRCC3 and NBS1 gene polymorphisms modulate the risk of pre-oral cancer and oral cancer in the North Indian population. Journal of cancer research and therapeutics 2023; 19(2): 304-11. 35. Nigam K, Gupta S, Gupta OP, Srivastav RK, Singh SP, Sanyal S. Alteration of the risk of pre-oral cancer and cancer in North Indian population by NAT1 and NAT2 polymorphisms genotypes and haplotypes. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery 2021; 278(10): 4081-9. 36. Nigam K, Yadav SK, Samadi FM, Bhatt ML, Gupta S, Sanyal S. Risk Modulation of Oral Pre Cancer and Cancer with Polymorphisms in XPD and XPG Genes in North Indian Population. Asian Pacific journal of cancer prevention : APJCP 2019; 20(8): 2397-403. 37. Farshbaf A, Mohajertehran F, Sahebkar A, Garmei Y, Sabbagh P, Mohtasham N. The role of altered microRNA expression in premalignant and malignant head and neck lesions with epithelial origin. Health science reports 2022; 5(6): e921. 38. Ge X, Xie H, Wang L, Li R, Zhang F, Xu J, et al. MicroRNA-122 promotes apoptosis of keratinocytes in oral lichen planus through suppressing VDR expression. Journal of cellular and molecular medicine 2021; 25(7): 3400-7. 39. Du J, Gao R, Wang Y, Nguyen T, Yang F, Shi Y, et al. MicroRNA-26a/b have protective roles in oral lichen planus. Cell death & disease 2020; 11(1): 15.