Association of vitamin D receptor FokI and ApaI polymorphisms with lung cancer risk in Tunisian population

Kaabachi, Wajih; Kaabachi, Safa; Rafrafi, Ahlem; Amor, Amira Ben; Tizaoui, Kalthoum; Sassi, Fayçal Haj; Hamzaoui, Kamel

doi:10.1007/s11033-014-3538-2

Cited by 25 publications

(22 citation statements)

References 42 publications

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“…It is worth noting that all the VDR genotypes were related to declined NSCLC risk. An increased risk comparing TT vs. CC in Taq1 in our study is consistent with the results observed in previous studies [50,51,52]. On the other hand, there are a few other studies that have also found no association with increased risk [53,54].…”

Section: Discussionsupporting

confidence: 93%

Vitamin D-Related Gene Polymorphisms, Plasma 25-Hydroxy-Vitamin D, Cigarette Smoke and Non-Small Cell Lung Cancer (NSCLC) Risk

Cheng

Yang

2016

IJMS

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Epidemiological studies regarding the relationship between vitamin D, genetic polymorphisms in the vitamin D metabolism, cigarette smoke and non-small cell lung cancer (NSCLC) risk have not been investigated comprehensively. To search for additional evidence, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and radioimmunoassay method were utilized to evaluate 5 single-nucleotide polymorphisms (SNPs) in vitamin D receptor (VDR), 6 SNPs in 24-hydroxylase (CYP24A1), 2 SNPs in 1α-hydroxylase (CYP27B1) and 2 SNPs in vitamin D-binding protein (group-specific component, GC) and plasma vitamin D levels in 426 NSCLC cases and 445 controls from China. Exposure to cigarette smoke was ascertained through questionnaire information. Multivariable linear regressions and mixed effects models were used in statistical analysis. The results showed that Reference SNP rs6068816 in CYP24A1, rs1544410 and rs731236 in VDR and rs7041 in GC were statistically significant in relation to reduction in NSCLC risk (p < 0.001–0.05). No significant connection was seen between NSCLC risk and overall plasma 25-hydroxyvitamin D [25(OH)D] concentrations, regardless of smoking status. However, the mutation genotype of CYP24A1 rs6068816 and VDR rs1544410 were also significantly associated with increased 25(OH)D levels only in both the smoker and non-smoker cases (p < 0.01–0.05). Meanwhile, smokers and non-smokers with mutated homozygous rs2181874 in CYP24A1 had significantly increased NSCLC risk (odds ratio (OR) = 2.14, 95% confidence interval (CI) 1.47–3.43; p = 0.031; OR = 3.57, 95% CI 2.66–4.74; p = 0.019, respectively). Smokers with mutated homozygous rs10735810 in VDR had significantly increased NSCLC risk (OR = 1.93, 95% CI 1.41–2.76; p = 0.015). However, smokers with mutated homozygous rs6068816 in CYP24A1 had significantly decreased NSCLC risk (OR = 0.43, 95% CI 0.27–1.02; p = 0.006); and smokers and non-smokers with mutated homozygous rs1544410 in VDR had significantly decreased NSCLC risk (OR = 0.51, 95% CI 0.34–1.17; p = 0.002; OR = 0.26, 95% CI 0.20–0.69; p = 0.001, respectively). There are significant joint effects between smoking and CYP24A1 rs2181874, CYP24A1 rs6068816, VDR rs10735810, and VDR rs1544410 (p < 0.01–0.05). Smokers with mutated homozygous rs10735810 in VDR had significantly increased NSCLC risk (OR = 1.93, 95% CI 1.41–2.76; p = 0.015). In summary, the results suggested that the lower the distribution of vitamin D concentration, the more the genetic variations in CYP24A1, VDR and GC genes may be associated with NSCLC risk. In addition, there are significant joint associations of cigarette smoking and vitamin D deficiency on NSCLC risk.

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Section: Discussionsupporting

confidence: 93%

Vitamin D-Related Gene Polymorphisms, Plasma 25-Hydroxy-Vitamin D, Cigarette Smoke and Non-Small Cell Lung Cancer (NSCLC) Risk

Cheng

Yang

2016

IJMS

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“…ii) A-C-T (rs1544410-rs7975232-rs731236) (OR 5 5.82, p 5 0.008). 13 Our results are consistent with the possible association of rs1544410-rs731236 (BsmI-TaqI) haplotype and lung cancer risk. Further investigation on a larger group of patients is needed to confirm this association with lung cancer risk.…”

Section: Discussionsupporting

confidence: 90%

“…In a recently report of 240 lung cancer patients and 280 healthy individuals from the North African population, Kaabachi et al showed a significantly increased risk of lung cancer among carriers of the rs2228570 (FokI) variant. There was no significant association with lung cancer risk of the rs1544410 (BsmI) and rs731236 (TaqI) 13 polymorphisms.…”

Section: Discussionmentioning

confidence: 88%

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

Gromowski

Gapska

Scott

et al. 2017

Intl Journal of Cancer

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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.

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“…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.…”

Section: Literature Searchmentioning

confidence: 99%

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

Li¹,

Liu²,

Liu³

et al. 2019

J. Cancer

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Purpose: The aim of this meta-analysis was to investigate polymorphism of Bsm1, Apal, Taq1 and Cdx-2 in vitamin D receptor (VDR) associations in relation to lung cancer (LC) susceptibility. Methods: 9 literatures were recruited into this meta-analysis from PubMed, PMC, Embase, Web of Science, Cochrane library and CNKI. STATA version 15.1 was used for statistical tests. The heterogeneity was tested using I 2 statistics. According to the value of I 2 , the random-effect model (REM) or fixed-effect model (FEM) was selected to combine data from studies, respectively. Potential publication bias was evaluated by Egger's test. Sensitivity analysis was also performed to evaluate the stability and reliability in results. Results: Decreased susceptibility of LC was found in all genetic models contrast in Bsm1 gene of VDR (a vs. A: OR = 0.62, 95 % CI = 0.44-0.87; aa vs. AA: OR = 0.76, 95 % CI = 0.60-0.96; Aa vs. AA: OR = 0.59, 95 % CI = 0.39-0.88; aa vs. AA+Aa: OR = 0.80, 95 % CI = 0.64-0.99; Aa+aa vs. AA: OR = 0.57, 95 % CI = 0.37-0.86). The similar results were also found in partial genetic models of Taq1 (a vs. A: OR = 0.88, 95 % CI = 0.79-0.98; aa vs. AA+Aa: OR = 0.84, 95 % CI = 0.73-0.98) and Cdx-2 (Aa vs. AA: OR = 0.80, 95 % CI = 0.66-0.98; Aa+aa vs. AA: OR = 0.79, 95 % CI = 0.65-0.96). Likewise, significant correlation between Bsm1, Taq1 polymorphism and LC risk was detected among Asians. Cdx-2 polymorphism was considered as a protective factor in Caucasians, whereas no association of Apal polymorphism with LC risk was observed in Asians and Caucasians for all genetic models. Conclusion: The results of this meta-analysis suggested that Bsm1, Taq1 and Cdx-2 polymorphism may contribute to lung cancer susceptibility, more studies need be conducted to confirm in the future.

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Association of vitamin D receptor FokI and ApaI polymorphisms with lung cancer risk in Tunisian population

Cited by 25 publications

References 42 publications

Vitamin D-Related Gene Polymorphisms, Plasma 25-Hydroxy-Vitamin D, Cigarette Smoke and Non-Small Cell Lung Cancer (NSCLC) Risk

Vitamin D-Related Gene Polymorphisms, Plasma 25-Hydroxy-Vitamin D, Cigarette Smoke and Non-Small Cell Lung Cancer (NSCLC) Risk

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

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

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