Generic placeholder image

Combinatorial Chemistry & High Throughput Screening


ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Review Article

The Association of Vitamin D Receptor Gene Polymorphism with Lung Cancer Risk: An Update Meta-analysis

Author(s): Zhi-Hong Yu, Miao Chen, Qing-Qian Zhang and Xun Hu*

Volume 21 , Issue 10 , 2018

Page: [704 - 710] Pages: 7

DOI: 10.2174/1386207322666190125150557

Price: $65


The association between vitamin D receptor (VDR) genetic polymorphism and lung cancer risk has been evaluated by the previous meta-analyses. Due to the emergence of novel studies and inappropriate inclusion of overlapping populations, an updated meta-analysis on recent evidences is necessarily needed. We comprehensively searched databases of PubMed, Web of Science and Chinese National Knowledge Infrastructure and finally obtained 7 eligible studies according to the inclusion criteria. Four positions on VDR gene, namely ApaI (rs7975232), BsmI (rs1544410), FokI (rs10735810) and TaqI (rs731236), were considered in this investigation. Data pooling found no significant association of lung cancer risk with ApaI or FokI. In contrast, it was indicated that the BsmI A allele was negatively related to the lung cancer risk, compared with the G allele (OR = 0.51, 95% CI = 0.33-0.79). Individuals with BsmI AA (OR = 0.53, 95% CI = 0.26-1.11) and AG genotypes (OR = 0.46, 95% CI = 0.30−0.71) showed decreased risk of lung cancer, compared with those of GG genotype. Regarding the TaqI polymorphism, the T allele carriers were at increased risk of lung cancer (OR = 1.25, 95% CI = 1.04-1.50). Compared with the TaqI TC+CC genotype, the TT genotype was positively associated with lung cancer risk (OR = 1.42, 95% CI = 1.11-1.82). No publication bias was identified in any of the analysis. In conclusion, VDR genetic polymorphism may be correlated to lung cancer risk. Given limited number of the included studies, more observations are warranted to draw a safer conclusion.

Keywords: Vitamin D receptor, lung cancer, genetic polymorphism, meta-analysis, risk, meta-analyses.

Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2016. CA Cancer J. Clin., 2016, 66(1), 7-30.
Doll, R.; Peto, R.; Boreham, J.; Sutherland, I. Mortality in relation to smoking: 50 years’ observations on male British doctors. BMJ, 2004, 328(7455), 1519.
Malhotra, J.; Malvezzi, M.; Negri, E.; La Vecchia, C.; Boffetta, P. Risk factors for lung cancer worldwide. Eur. Respir. J., 2016, 48(3), 889-902.
Christakos, S.; Dhawan, P.; Verstuyf, A.; Verlinden, L.; Carmeliet, G.; Vitamin, D. Metabolism, molecular mechanism of action, and pleiotropic effects. Physiol. Rev., 2016, 96(1), 365-408.
Bandera Merchan, B.; Morcillo, S.; Martin-Nuñez, G.; Tinahones, F.J.; Macías-González, M. The role of vitamin D and VDR in carcinogenesis: Through epidemiology and basic sciences. J. Steroid Biochem. Mol. Biol., 2017, 167, 203-218.
Vaughan-Shaw, P.G.; O’Sullivan, F.; Farrington, S.M.; Theodoratou, E.; Campbell, H.; Dunlop, M.G.; Zgaga, L. The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: Systematic review and meta-analysis. Br. J. Cancer, 2017, 116(8), 1092-1110.
Zella, L.A.; Kim, S.; Shevde, N.K.; Pike, J.W. Enhancers located within two introns of the vitamin D receptor gene mediate transcriptional autoregulation by 1,25-dihydroxyvitamin D3. Mol. Endocrinol., 2006, 20(6), 1231-1247.
Santagata, S.; Thakkar, A.; Ergonul, A.; Wang, B.; Woo, T.; Hu, R.; Harrell, J.C.; McNamara, G.; Schwede, M.; Culhane, A.C.; Kindelberger, D.; Rodig, S.; Richardson, A.; Schnitt, S.J.; Tamimi, R.M.; Ince, T.A. Taxonomy of breast cancer based on normal cell phenotype predicts outcome. J. Clin. Invest., 2014, 124(2), 859-870.
Berlanga-Taylor, A.J.; Knight, J.C. An integrated approach to defining genetic and environmental determinants for major clinical outcomes involving vitamin D. Mol. Diagn. Ther., 2014, 18(3), 261-272.
Bi, X.B. Vitamin D receptor gene polymorphism and genetic susceptibility of nonsmall cell lung cancer. J. Trop. Med., 2016, 16(7), 905-908.
Dogan, I.; Onen, H.I.; Yurdakul, A.S.; Konac, E.; Ozturk, C.; Varol, A.; Ekmekci, A. Polymorphisms in the vitamin D receptor gene and risk of lung cancer. Med. Sci. Monit., 2009, 15(8), BR232-BR242.
Kaabachi, W.; Kaabachi, S.; Rafrafi, A.; Amor, A.B.; Tizaoui, K.; Haj Sassi, F.; Hamzaoui, K. Association of vitamin D receptor FokI and ApaI polymorphisms with lung cancer risk in Tunisian population. Mol. Biol. Rep., 2014, 41(10), 6545-6553.
Li, R. Relationship between vitamin D receptor gene rs7975232 single nucleotide polymorphism and lung cancer risk. Chinas. Med., 2013, 8(10), 1390-1392.
Wei, M.D.; Su, G-S.; Ling, Z.G.; Wei, S.Q.; Guangxi, L. Clinical study effection of vitamin D receptor gene polymorphism on the susceptibility of lung squamous cell carcinoma, and chemotherapy curative. Chronic Pathematol. J., 2014, 15(5), 349-351.
Wu, X.; Cheng, J.; Yang, K. Vitamin D-related gene polymorphisms, plasma 25-hydroxy-vitamin d, cigarette smoke and non-small cell lung cancer (NSCLC) risk. Int. J. Mol. Sci., 2016, 17(10), E1597.
Yang, H.; Zhou, W.; Tang, J.; Qi, Z.M.; Hou, Y.Y.; Cai, L.; Pan, F.D.; Peng, Y. The interactive influence of Vitamin D receptor genetic polymorphism and smoking on non-small-cell lung cancer. Chinese J. Gerontol., 2013, 33(16), 3844-3846.
Fu, Y.; Li, J.; Zhang, Y. Polymorphisms in the vitamin D receptor gene and the lung cancer risk. Tumour Biol., 2014, 35(2), 1323-1330.
Zhong, H.; Zhou, R.; Feng, Y.; Zheng, G.X.; Liang, Y.; Zhang, J.Y.; Qin, X.Q.; Chen, W.; Wu, J.Q.; Zhong, Y.H. Association of vitamin D receptor gene polymorphism with the risk of lung cancer: A meta-analysis. J. Recept. Signal Transduct. Res., 2014, 34(6), 500-505.
Xu, J.; Turner, A.; Little, J.; Bleecker, E.R.; Meyers, D.A. Positive results in association studies are associated with departure from Hardy-Weinberg equilibrium: Hint for genotyping error? Hum. Genet., 2002, 111(6), 573-574.
Cai, L.N.; Yang, Y.H.; Qi, Z.M.; Fu, Z.Z.; Tang, L.J.; Yu, Z.Y. The relationship between vitamin D receptor gene BmsI sites polymorphisms and hereditary susceptibility to non-small-cell lung cancer. Chin. J. Coal Ind. Med., 2012, 15(3), 321-324.
Tang, L.J.; Yang, Y.H.; Cai, L.; Yu, Z.G. QiI, Z.M.; Fu, Z.Z. Association of vitamin D receptor BsmI and TaqI polymorphisms with non-small-cell lung cancer risk. Shandong Med. J., 2012, 52(43), 40-41.
Gandini, S.; Gnagnarella, P.; Serrano, D.; Pasquali, E.; Raimondi, S. Vitamin D receptor polymorphisms and cancer. Adv. Exp. Med. Biol., 2014, 810, 69-105.
Xiong, L.; Cheng, J.; Gao, J.; Wang, J.; Liu, X.; Wang, L. Vitamin D receptor genetic variants are associated with chemotherapy response and prognosis in patients with advanced non-small-cell lung cancer. Clin. Lung Cancer, 2013, 14(4), 433-439.
Heist, R.S.; Zhou, W.; Wang, Z.; Liu, G.; Neuberg, D.; Su, L.; Asomaning, K.; Hollis, B.W.; Lynch, T.J.; Wain, J.C.; Giovannucci, E.; Christiani, D.C. Circulating 25-hydroxyvitamin D, VDR polymorphisms, and survival in advanced non-small-cell lung cancer. J. Clin. Oncol., 2008, 26(34), 5596-5602.
Kilkkinen, A.; Knekt, P.; Heliövaara, M.; Rissanen, H.; Marniemi, J.; Hakulinen, T.; Aromaa, A. Vitamin D status and the risk of lung cancer: A cohort study in Finland. Cancer Epidemiol. Biomarkers Prev., 2008, 17(11), 3274-3278.
Zhou, W.; Heist, R.S.; Liu, G.; Asomaning, K.; Neuberg, D.S.; Hollis, B.W.; Wain, J.C.; Lynch, T.J.; Giovannucci, E.; Su, L.; Christiani, D.C. Circulating 25-hydroxyvitamin D levels predict survival in early-stage non-small-cell lung cancer patients. J. Clin. Oncol., 2007, 25(5), 479-485.
Van Renterghem, D. Lung cancer survival: vitamin D could be just a marker of physical fitness. J. Clin. Oncol, 2007. 25(34), 5537-5538; (author reply 5538-5539).

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy