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ORIGINAL ARTICLE
Year : 2018  |  Volume : 14  |  Issue : 4  |  Page : 820-825

Relationship between Vitamin D receptor gene polymorphism and renal cell carcinoma susceptibility


1 Department of Nephrology, The Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China
2 Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China

Date of Web Publication27-Jun-2018

Correspondence Address:
Wei-Ji Xie
Department of Nephrology, The Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.231425

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 > Abstract 


Aim of Study: Results on the association of Vitamin D receptor (VDR) gene polymorphism with renal cell carcinoma (RCC) susceptibility from the present reports are still debating. This meta-analysis was conducted to assess the association of VDR ApaI (rs7975232), BsmI (rs1544410), TaqI (rs731236), and Fok1 (rs2228570) gene polymorphisms with RCC risk.
Materials and Methods: The association studies were recruited from PubMed on May 1, 2016, and eligible reports were extracted and data were synthesized using meta-analysis method.
Result: Six investigations were included into this meta-analysis for the relationship between VDR gene polymorphism and RCC susceptibility. In this meta-analysis, the ApaI A allele, AA genotype, aa genotype, and Fok1 FF genotype were associated with RCC susceptibility in Asians. However, VDR BsmI and TaqI gene polymorphisms were not associated with the RCC risk in Asians, Caucasians, and overall populations. Furthermore, Fok1 gene polymorphism was not associated with the RCC risk in Caucasians and overall populations.
Conclusion: ApaI gene polymorphism and Fok1 FF genotype were associated with RCC susceptibility in Asians.

Keywords: ApaI (rs7975232), BsmI (rs1544410), Fok1 (rs2228570), gene polymorphism, meta-analysis, renal cell carcinoma, TaqI (rs731236), Vitamin D receptor


How to cite this article:
Lin ZJ, Zhang XL, Yang ZS, She XY, Xie Y, Xie WJ. Relationship between Vitamin D receptor gene polymorphism and renal cell carcinoma susceptibility. J Can Res Ther 2018;14:820-5

How to cite this URL:
Lin ZJ, Zhang XL, Yang ZS, She XY, Xie Y, Xie WJ. Relationship between Vitamin D receptor gene polymorphism and renal cell carcinoma susceptibility. J Can Res Ther [serial online] 2018 [cited 2019 Nov 22];14:820-5. Available from: http://www.cancerjournal.net/text.asp?2018/14/4/820/231425




 > Introduction Top


Renal cell carcinoma (RCC) is one of the most common renal malignancies in adults, and metastatic disease is relatively common at presentation and frequently involves the lung, bone, brain, liver, and adrenal glands.[1] There is a 30–40% risk of recurrence, and a 10% risk of developing metastatic disease after 5 years.[1] There lacks a well-documented diagnostic approach to predict the risk of RCC, and the etiology of RCC is not clear. The current evidence shows that some gene polymorphisms are associated with the RCC susceptibility.

Vitamin D activity is controlled by Vitamin D receptor (VDR), which is affected by different genetic polymorphisms, including ApaI (rs7975232), BsmI (rs1544410), TaqI (rs731236), and Fok1 (rs2228570) restriction fragment length polymorphisms, which have been reported to be associated with several diseases.[2] Gene polymorphism has been reported to be an important factor which increases the RCC susceptibility. We conducted this meta-analysis to investigate whether the VDR ApaI (rs7975232), BsmI (rs1544410), TaqI (rs731236), and Fok1 (rs2228570) gene polymorphisms was associated with the RCC susceptibility.


 > Materials and Methods Top


Search strategy

Relevant reports were searched from the electronic databases of PubMed on May 1, 2016. Retrieval strategy using “(Vitamin D receptor OR VDR) and (renal cell carcinoma)” was entered into PubMed. The additional reports were identified and included through references cited in recruited articles.

Inclusion and exclusion criteria

Inclusion criteria

  1. The outcome of the study had to be RCC
  2. There were two comparison groups at least (RCC group vs. control group)
  3. Investigation should provide the genotype distribution data of VDR.


Exclusion criteria

  1. Case reports, review articles, and editorials
  2. Preliminary result was not on VDR gene polymorphism or RCC
  3. Investigating the role of VDR gene expression to diseases.


Data extraction and synthesis

The following information from each eligible study was extracted independently by two investigators: first author's surname, year of publication, location of the study performed, control source of the control group, and the number of cases and controls for VDR genotypes. The results were compared, and disagreement was resolved by discussion.

Statistical analysis

Cochrane Review Manager version 5 (Cochrane Library, UK) was used for this meta-analysis to calculate the available data from each study. The pooled statistic was calculated using the fixed effects model, but a random effects model was conducted when the P value of heterogeneity test was <0.1. Results were expressed with odds ratios (ORs) for dichotomous data, and 95% confidence intervals (CI) were also calculated. P < 0.05 was required for the pooled OR to be statistically significant. I2 was used to test the heterogeneity among the included studies.


 > Results Top


Study characteristics

Six investigations were included for the relationship between VDR gene polymorphism and RCC susceptibility in this meta-analysis [Table 1]. The data of our interest were extracted [Table 1]. Two studies [3],[4] were for VDR ApaI (rs7975232) gene polymorphism, four studies [3],[4],[5],[6] were for BsmI (rs1544410) gene polymorphism, four studies [3],[4],[5],[7] were for TaqI (rs731236) gene polymorphism, and four studies [4],[5],[6],[8] were for Fok1 (rs2228570) gene polymorphism.
Table 1: Characteristics of the studies about the effects of Vitamin D receptor gene polymorphism on renal cell carcinoma risk

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Relationship between Vitamin D receptor ApaI gene polymorphism and renal cell carcinoma risk

All the included studies were from Asian populations. VDR ApaI A allele, AA genotype, and aa genotype were found to be associated with RCC risk in Asians in this meta-analysis [A allele: OR = 1.41, 95% CI: 1.15–1.72, P = 0.0007; AA genotype: OR = 2.25, 95% CI: 1.41–3.60, P = 0.0007; aa genotype: OR = 0.72, 95% CI: 0.55–0.94, P = 0.01; [Figure 1] and [Table 2].
Figure 1: Association of Vitamin D receptor ApaI gene polymorphism with renal cell carcinoma susceptibility in overall populations

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Table 2: Meta-analysis of the association of Vitamin D receptor gene polymorphism with renal cell carcinoma risk

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Relationship between Vitamin D receptor BsmI gene polymorphism and renal cell carcinoma risk

In this meta-analysis, VDR BsmI B allele, BB genotype, and bb genotype were reported to be not associated with RCC susceptibility in overall populations [B allele: OR = 0.88, 95% CI: 0.67–1.16, P = 0.38; BB genotype: OR = 0.83, 95% CI: 0.65–1.05, P = 0.12; bb genotype: OR = 1.21, 95% CI: 0.79–1.85, P = 0.37; [Figure 2] and [Table 2].
Figure 2: Association of Vitamin D receptor BsmI gene polymorphism with renal cell carcinoma susceptibility in overall populations

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In subgroup analysis by ethnicity, there was no association between VDR BsmI gene polymorphism and RCC risk for Asians and Caucasian population [Table 2].

Relationship between Vitamin D receptor TaqI gene polymorphism and renal cell carcinoma risk

In this meta-analysis, VDR TaqI t allele, tt genotype, and TT genotype were not associated with RCC susceptibility in overall populations [t allele: OR = 0.86, 95% CI: 0.59–1.26, P = 0.44; tt genotype: OR = 0.84, 95% CI: 0.64–1.10, P = 0.20; TT genotype: OR = 1.16, 95% CI: 0.75–1.78, P = 0.50; [Figure 3] and [Table 2]. t allele, tt genotype, and TT genotype were not found to be associated with the risk of RCC for Asian population and Caucasians [Table 2].
Figure 3: Association of Vitamin D receptor TaqI gene polymorphism with renal cell carcinoma susceptibility in overall populations

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Relationship between Vitamin D receptor Fok1 gene polymorphism and renal cell carcinoma risk

VDR Fok1 f allele, ff genotype, and FF genotype were not found to be associated with RCC risk in overall populations [f allele: OR = 1.05, 95% CI: 0.85–1.29, P = 0.64; ff genotype: OR = 0.99, 95% CI: 0.83–1.18, P = 0.90; FF genotype: OR = 0.91, 95% CI: 0.66–1.26, P = 0.57; [Figure 4] and [Table 2].
Figure 4: Association of Vitamin D receptor Fok1 gene polymorphism with renal cell carcinoma susceptibility in overall populations

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In Asian population, f allele was associated with the risk of RCC, but ff genotype and FF genotype were not [Table 2]. However, BsmI f allele, ff genotype, and FF genotype were not found to be associated with RCC risk in Caucasians [Table 2].


 > Discussion Top


In this study, six investigations were included in this meta-analysis for the relationship between VDR gene polymorphism and RCC susceptibility. In this meta-analysis, the ApaI A allele, AA genotype, aa genotype, and Fok1 FF genotype were associated with RCC susceptibility in Asians. However, VDR BsmI and TaqI gene polymorphisms were not associated with the RCC risk in Asians, Caucasians, and overall populations. Furthermore, Fok1 gene polymorphism was not associated with the RCC risk in Caucasians and overall populations.

In previous, Ou et al.[9] performed a meta-analysis and reported that the ApaI AA genotype, BsmI BB genotype, Fok1 f allele, and Fok1 FF genotype were associated with the risk of RCC in Asians. However, VDR ApaI, BsmI, TaqI, and Fok1 gene polymorphisms were not associated with the risk of RCC in overall populations and Caucasians. In this study, we included more studies for meta-analysis and reported that the ApaI A allele, AA genotype, aa genotype, and Fok1 FF genotype were associated with RCC susceptibility in Asians. However, other associations were not found in our meta-analysis. Results from our meta-analysis might be more robust to some extent.

There were some meta-analyses to assess the relationship between VDR gene polymorphism and cancers susceptibility. Lu et al.[10] performed a meta-analysis including eight studies, and the estimated VDR polymorphism showed no significant association between Bsm1, Taq1, Apa1 polymorphism, and breast cancer risk. Yu et al.[11] conducted a meta-analysis including 14 case–control studies and suggested that the VDR BsmI polymorphism might be associated with a moderate protective effect against colorectal cancer. Zhong et al.[12] recruited six reports into their meta-analysis and indicated that B allele bb genotype t allele and TT genotype were associated with lung cancer risk in overall populations. AA genotype, B allele, BB genotype, and bb genotype were associated with the risk of lung cancer in Asians. Furthermore, bb genotype, t allele, and TT genotype were associated with lung cancer risk in Caucasians.

In our meta-analysis, the ApaI A allele, AA genotype, aa genotype, and Fok1 FF genotype might become a valuable indicator to predict the RCC risk in Asians. However, those findings should be regarded cautiously because various other ingredients, such as small sample size, heterogeneity of enrolled cases, limited statistical power, variable study designs, and different interventions, were related to affect the results closely.


 > Conclusion Top


The ApaI A allele, AA genotype, aa genotype, and Fok1 FF genotype were associated with RCC susceptibility in Asians. However, more studies should be conducted to confirm it.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

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Vo E, Palacio CH, Omino R, Link RE, Sada Y, Avo A. Solitary colon metastasis from renal cell carcinoma nine years after nephrectomy: A case report. Int J Surg Case Rep 2016;27:55-58.  Back to cited text no. 1
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Al-Eisa AA, Haider MZ. Vitamin D receptor gene TaqI and Apal polymorphisms and steroid responsiveness in childhood idiopathic nephrotic syndrome. Int J Nephrol Renovasc Dis 2016;9:187-92.  Back to cited text no. 2
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Obara W, Suzuki Y, Kato K, Tanji S, Konda R, Fujioka T. Vitamin D receptor gene polymorphisms are associated with increased risk and progression of renal cell carcinoma in a Japanese population. Int J Urol 2007;14:483-7.  Back to cited text no. 3
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Yang C, Li J, Li Y, Wu D, Sui C, Jiang Y, et al. The Vitamin D receptor gene ApaI polymorphism is associated with increased risk of renal cell carcinoma in Chinese population. Sci Rep 2016;6:25987.  Back to cited text no. 4
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Karami S, Brennan P, Hung RJ, Boffetta P, Toro J, Wilson RT, et al. Vitamin D receptor polymorphisms and renal cancer risk in Central and Eastern Europe. J Toxicol Environ Health A 2008;71:367-72.  Back to cited text no. 5
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Ikuyama T, Hamasaki T, Inatomi H, Katoh T, Muratani T, Matsumoto T. Association of Vitamin D receptor gene polymorphism with renal cell carcinoma in Japanese. Endocr J 2002;49:433-8.  Back to cited text no. 7
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Southard EB, Roff A, Fortugno T, Richie JP Jr., Kaag M, Chinchilli VM, et al. Lead, calcium uptake, and related genetic variants in association with renal cell carcinoma risk in a cohort of male Finnish smokers. Cancer Epidemiol Biomarkers Prev 2012;21:191-201.  Back to cited text no. 8
    
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Ou C, Zhao HL, Zhu B, Huang LS, Li PZ, Lao M. Association of Vitamin D receptor gene polymorphism with the risk of renal cell carcinoma: A meta-analysis. J Recept Signal Transduct Res 2014;34:463-8.  Back to cited text no. 9
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Lu D, Jing L, Zhang S. Vitamin D receptor polymorphism and breast cancer risk: A meta-analysis. Medicine (Baltimore) 2016;95:e3535.  Back to cited text no. 10
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Yu K, Yang J, Jiang Y, Song R, Lu Q. Vitamin D receptor BsmI polymorphism and colorectal cancer risk: An updated analysis. Asian Pac J Cancer Prev 2014;15:4801-7.  Back to cited text no. 11
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Zhong H, Zhou R, Feng Y, Zheng GX, Liang Y, Zhang JY, et al. Association of Vitamin D receptor gene polymorphism with the risk of lung cancer: A meta-analysis. J Recept Signal Transduct Res 2014;34:500-5.  Back to cited text no. 12
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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
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