Role of proinflammatory cytokines on expression of vitamin D metabolism and target genes in colon cancer cells

Hummel, Doris M.; Fetahu, Irfete S.; Gröschel, Charlotte; Manhardt, Teresa; Kállay, Enikö

doi:10.1016/j.jsbmb.2013.09.017

Cited by 51 publications

(38 citation statements)

References 33 publications

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“…This might be attributed to CYP24A1 being increased in NSCLC tumors. Several studies have already examined the gain of 20q in gastro-esophageal junction [40], colon [41], breast [42], prostate [43], head and neck [44] as well as lung tumors [45,46]. Kong et al reported that CYP24A1 can reduce the 25(OH)D level and potentially increase NSCLC risk in cases with kinds of CYP24A1 polymorphisms [47].…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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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“…The renal vitamin D-activating enzyme 1 α -hydroxylase (CYP27B1) is mainly regulated by serum PTH and FGF23, but extra renal production of 1,25(OH) 2 D by CYP247B1 is known to be induced by inflammatory cytokines such as TNF- α [36–39]. Further characterization of this novel component of vitamin D and inflammation will be important in future studies of vitamin D and inflammation in the elderly, especially in those with increased inflammatory disease activity such as RA patients [40].…”

Section: Discussionmentioning

confidence: 99%

Associations of total and free 25OHD and 1,25(OH)2D with serum markers of inflammation in older men

et al. 2016

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Summary Vitamin D is hypothesized to suppress inflammation. We tested total and free vitamin D metabolites and their association with inflammatory markers. Interleukin-6 levels were lower with higher 25-hydroxyvitamin D. 1,25-dihydroxyvitamin D and free 25OHD associations mirrored those of 25OHD. However, associations for the two metabolites diverged for tumor necrosis factor alpha (TNF-α) soluble receptors. Introduction Vitamin D is hypothesized to suppress inflammation, and circulating 25-hydroxyvitamin D (25OHD) and inflammatory markers are inversely correlated. However, total serum 25OHD may not be the best indicator of biologically active vitamin D. Methods We tested serum total 25OHD, total 1,25(OH)2D, vitamin D binding protein (DBP), and estimated free 25OHD and free 1,25(OH)2D associations with inflammatory markers serum interleukin-6 (IL-6), TNF-α and their soluble receptors, interleukin-10 (IL-10), and C-reactive protein (CRP) as continuous outcomes and the presence of ≥2 inflammatory markers in the highest quartile as a dichotomous outcome, in a random subcohort of 679 men in the Osteoporotic Fractures in Men (MrOS) study. Results IL-6 was lower in men with higher 25OHD (−0.23 μg/mL per standard deviation (SD) increase in 25OHD, 95 % confidence intervals (CI) −0.07 to −0.38 μg/mL) and with higher 1,25(OH)2D (−0.20 μg/mL, 95 % CI −0.0004 to −0.39 μg/mL); free D associations were slightly stronger. 25OHD and DBP, but not 1,25(OH)2D, were independently associated with IL-6. TNF-α soluble receptors were inversely associated with 1,25(OH)2D but positively associated with 25OHD, and each had independent effects. The strongest association with ≥2 inflammatory markers in the highest quartile was for free 1,25(OH)2D (odds ratios (OR) 0.70, 95 % CI 0.54 to 0.89 per SD increase in free 1, 25(OH)2D). Conclusions Associations of 1,25(OH)2D and free 25OHD with IL-6 mirrored those of 25OHD, suggesting that 1, 25(OH)2D and free D do not improve upon 25OHD in population-based IL-6 studies. However, associations for the two metabolites diverged for TNF-α soluble receptor, warranting examination of both metabolites in studies of TNF-α and its antagonists.

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“…It should be stressed however, that IL-6 and TNF-α, two pro-inflammatory cytokines that are crucial for development of inflammatory bowel disease and colorectal cancer, may impair the anti-inflammatory activity of vit. D [98] . The prospect that vit.…”

Section: α 25-dihydroxyvitamin D3mentioning

confidence: 99%

Modulators affecting the immune dialogue between human immune and colon cancer cells

Djaldetti¹

2014

WJGO

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Role of proinflammatory cytokines on expression of vitamin D metabolism and target genes in colon cancer cells

Cited by 51 publications

References 33 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

Associations of total and free 25OHD and 1,25(OH)2D with serum markers of inflammation in older men

Modulators affecting the immune dialogue between human immune and colon cancer cells

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