Serum 25(OH)D concentration, common variants of the VDR gene and lung cancer occurrence

Abstract

The first aim of our study was to examine the association between common variants in VDR [rs2228570 (FokI), rs1544410 (BsmI), rs7975232 (ApaI), rs731236 (TaqI) and rs11568820 (Cdx2)] and lung cancer risk in the Polish population. Genotyping and statistical analysis which included Chi-square test with Yates correction and haplotype frequency analysis were performed on a series of 840 consecutively collected lung cancer patients and 920 healthy controls. The second aim was to evaluate the link between serum 25(OH)D concentration and the number of lung cancers in a subgroup of 200 patients. A separate control group that consisted of 400 matched (by age, sex, smoking habits and the season of blood collection) healthy individuals was used to avoid posterior adjustment on the matched variables. Statistical analysis with the use of Chi-square test with Yates was performed. We found no statistically significant difference in the distribution of the allels of studied VDR variants among cases and controls. A statistically significant over-representation of VDR haplotypes: rs731236_A + rs1544410_T [odds ratio (OR) = 2.43, 95% confidence interval (CI) = 1.11-5.32, p < 0.001], rs731236_G + rs1544410_T (OR = 1.54, 95% CI = 1.31-1.81, p < 0.001) and rs731236_G + rs1544410_C (OR = 0.04, 95% CI = 0.03-0.07, p < 0.001) was detected. We found a tendency toward an increased number of lung cancers among individuals with low serum levels of 25(OH)D. To answer the question, whether VDR can be regarded as lung cancer susceptibility gene and low 25(OH)D serum levels is associated with lung cancer occurrences, additional, multicenter study needs to be performed.

Repurposing vitamin D for treatment of human malignancies via targeting tumor microenvironment

“…In addition, the incidences of other types of cancer ( e.g. , lung cancer, ovarian cancer, and melanoma) showed controversial outcomes or indeterminate results between 25(OH)D concentrations and cancer risk, and the association might be varied in different cancers 53 , 54 , 55 .…”

The Association BetweenVDRandGCPolymorphisms and Lung Cancer Risk: A Systematic Review and Meta-Analysis

“…Figure 1 showed the flow diagram of literature search and selection process. The 15 included articles were conducted in 5 countries: Turkey (Dogan et al, 2009;C xiçek et al, 2017), China (Li et al, 2013;Yang et al, 2013Yang et al, , 2017Liu et al, 2014;Wei et al, 2014;Hou, 2015;Kong et al, 2015;Bi et al, 2016;Wu et al, 2016;Wensheng et al, 2018), Tunisia (Kaabachi et al, 2014), Thailand (Maneechay et al, 2015), and Poland (Gromowski et al, 2017). Seven of the articles were written in English, and 8 were in Chinese; and 11 were performed in Asian populations, and 4 performed in Caucasian populations.…”

Association between Polymorphisms of Vitamin D Receptor and Lung Cancer Susceptibility: Evidence from an Updated Meta-analysis

“…The remaining 9 literatures were included in this meta-analysis because accordance with the inclusion criteria. [24,[26][27][28][29][30][31][32][33] The flow chart of literature selection process is shown in Figure 1.…”

“…In the pooled analysis, statistically significant protection role of Bsm1 (rs1544410 G>A) polymorphism in LC was observed among allele model, homozygous and heterozygous models and all genetic models (a vs. A: OR = 0.62, 95 % CI = 0.44-0.87, P = 0.005; aa vs. AA: OR = 0.76, 95 % CI = 0.60-0.96, P = 0.019; Aa vs. AA: OR = 0.59, 95 % CI = 0.39-0.88, P = 0.010; aa vs. AA+Aa: OR = 0.80, 95 % CI = 0.64-0.99, P = 0.039; Aa+aa vs. AA: OR = 0.57, 95 % CI = 0.37-0.86, P = 0.007). [26] *** * ** 7 Cai, 2012 [27] **** * ** 8 Yang, 2013 [28] *** * ** 7 Kaabachi, 2014 [29] *** * ** 7 Wu, 2016 [30] **** * ** 8 Bi, 2016 [31] **** * ** 8 Yang, 2017 [32] *** * ** 7 Gromowski, 2017 [24] **** * ** 8 Hülya Kanbur, 2018 [33] ** * ** 6 *indicates points of score Similar results were also found in partial genetic models of Taq1 (rs731236 T>C, a vs. A: OR = 0.88, 95 % CI = 0.79-0.98, P = 0.017; aa vs. AA+Aa: OR = 0.84, 95 % CI = 0.73-0.98, P = 0.022) and Cdx-2 (rs11568820 T>C, Aa vs. AA: OR = 0.80, 95 % CI = 0.66-0.98, P = 0.032; Aa+aa vs. AA: OR = 0.79, 95 % CI = 0.65-0.96, P = 0.018) (Table 3, Figure 2, Figure 3, Figure 4). No statistically significant association were found between Apa1 (rs7975232 C>A) gene polymorphism and LC.…”

“…[18,19] Studies have shown that 1,25-D3 and the VDR suppress c-MYC function via regulating the c-MYC/MXD1 network, providing a molecular basis for cancer preventive actions of vitamin D. [20] Variants of VDR was found associate with tuberculosis, [21] osteoporosis [22] and cancers including colorectal cancer and LC. [23,24] Until now, certain VDR gene variants have been verified in relation to LC risk with different results including Fok1, Bsm1, Taq1, Apa1, Cdx2. In order to further provide theoretical support for the pathogenesis of LC, explore the association between Bsm1 (rs1544410 G>A), Apa1 (rs7975232 C>A), Taq1 (rs731236 T>C) and Cdx-2 (rs11568820 T>C) polymorphisms of VDR associations in relation to LC susceptibility was performed in this meta-analysis of 9 related studies.…”