The role of Vitamin D Receptor gene polymorphisms in colorectal cancer risk

Messaritakis, Ippokratis; Koulouridi, Asimina; Sfakianaki, Maria; Gouvas, Nikolaos; Athanasakis, Elias; Tsiaoussis, Ioannis; Xynos, Evangelos; Mavroudis, Dimitris; Tzardi, Maria; Souglakos, John

doi:10.21203/rs.2.10883/v1

Cited by 5 publications

(12 citation statements)

References 40 publications

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“…As described previously by our group and others, TLR and VDR polymorphisms have been significantly associated with cancer development, progression, and, therefore, patients' clinical outcome [18,19,49,50]. Linked to the fact that TLR and the VDR genes play an important role in the prevention and elimination of infections, their mutations result in the impaired activation of these receptors, decreased response to microbial particles, and impaired homeostasis, thus leading to carcinogenesis and disease progression [51][52][53][54][55][56].…”

Section: Discussionmentioning

confidence: 91%

“…TLR2 (−196 to −174 bp), TLR4 (Asp299Gly and Thr399Ile), and TLR9 (T1237C and T1486C) polymorphisms and TaqI, ApaI, FokI, and BsmI polymorphisms of the VDR gene have been described previously [18,19], and their correlation with the presence of microbial DNA in the blood of CRC patients was investigated ( Table 3). A significant coexistence was observed between the detection of all four different microbial DNA fragments with all different VDR and TLR polymorphisms.…”

Section: Correlation Of Microbial Dna Presence and Tlr And Vdr Polymomentioning

confidence: 99%

“…Its development has been widely associated with genetic mutations, diet, inflammatory conditions, and dysbiosis [17]. The secondary objective of the study was to determine the correlation of the presence of, previously investigated by our group, toll-like receptors (TLRs) [18] and vitamin D receptors (VDRs) polymorphisms [19] with the detection of microbial DNA fragments in the blood of CRC patients. Table 1 and Data S1 summarize the demographics of all CRC patients enrolled in the study.…”

Section: Introductionmentioning

confidence: 99%

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The Prognostic Value of the Detection of Microbial Translocation in the Blood of Colorectal Cancer Patients

Messaritakis

Vogiatzoglou

Tsantaki

et al. 2020

Cancers

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Dysbiosis has been associated with various diseases and is of major health importance. Dysbiosis leads to microbial translocation, which is the passage of microorganisms, their fragments, or their metabolites from the intestinal lumen into the blood circulation and other sites. The aim of the study was to determine whether microbial translocation occurs in stage II/III-IV colorectal cancer (CRC) patients. The aim was also to evaluate the usefulness of blood PCR for diagnosis of such translocation and correlate the presence of toll-like receptor/vitamin D receptor (TLR/VDR) gene polymorphisms with microbial DNA fragments detected in the blood of CRC patients. Three hundred and ninety-seven CRC patients enrolled in the study. Peripheral blood DNA was analyzed using PCR for the amplification of genomic DNA encoding 16S rRNA, the β-galactosidase gene of Escherichia coli, glutamine synthase gene of Bacteroides fragilis, and 5.8S rRNA of Candida albicans. Significantly higher rates of all microbial fragments, but E. coli, detected were observed in the CRC patients (p < 0.001); such detection of all four microbial fragments was also significantly associated with the metastatic disease (p < 0.001), leading to shorter survival rates (p < 0.001). Tumor location in the right colon also significantly correlated with shorter survival (p = 0.016). Individuals with homozygous mutant alleles of TLR/VDR polymorphisms had significantly higher detection rates of microbial DNA fragments. The detection of microbial DNA fragments in CRC patients highlighted the role of these microbes in cancer development, progression, and patients’ survival.

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Section: Discussionmentioning

confidence: 91%

Section: Correlation Of Microbial Dna Presence and Tlr And Vdr Polymomentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Prognostic Value of the Detection of Microbial Translocation in the Blood of Colorectal Cancer Patients

Messaritakis

Vogiatzoglou

Tsantaki

et al. 2020

Cancers

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“…The interaction of vitamin D with the immune system is the important factor that activates both inherent and acquired immune systems. In recent years, with increasing knowledge about the effects of vitamin D, researchers have studied its influence in a variety of diseases and different kinds of cancer [ 24 , 25 ]. The data indicates that vitamin D is involved in the regulation of immune responses for both innate and adaptive immunity.…”

Section: Discussionmentioning

confidence: 99%

Significant association between Taq1 gene polymorphism in vitamin D receptor and chronic spontaneous urticaria in the Northeast of Iran

et al. 2021

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Objective Chronic spontaneous urticaria (CSU) is defined as urticaria with an unknown etiology which persists for more than 6 weeks. CSU is an uncomfortable cutaneous condition that occurs due to an immune-mediated inflammatory reaction. Many studies have demonstrated that vitamin D deficiency and single-nucleotide polymorphisms in the vitamin D receptor (VDR) impact the immune response. In the current study, the frequency of the Taq1 polymorphism in the VDR gene were compared between patients with CSU and individuals without CSU. Methods In a case–control study, a group of CSU patients (n = 100) was compared with a group of healthy age- and gender-matched individuals as a control group (n =100) who visited our center between 2015 and 2017. After DNA extraction from EDTA-containing blood, polymerase chain reaction (PCR–RFLP) was used to determine the presence of the Taq1 polymorphism. Serum vitamin D levels were measured using ELISA method (Abcam, Cambridge, USA). Results Genotyping for Taq1 polymorphism showed that TT, Tt and tt genes frequency in the CSU group were 36%, 54%, and 10% respectively. The TT, Tt and tt genotypes had a distribution of 50%, 47% and 3% respectively in the control group. The mean serum vitamin D level in the CSU group was 19.88 ± 8.14 ng/ml, which was not significantly correlated with the Taq1 polymorphism (P = 0.841). There was a significant relationship between Taq1 gene polymorphism (tt genotype) and CSU (P = 0.038). Tt genotype increased the risk of CSU (odds ratio = 1.596), and inheritance of tt genotype increased the risk even further (odds ratio = 4.630). Conclusion The frequency of Taq1 genotype polymorphism in the VDR gene was significantly higher in patients with CSU compared to the control group. The tt genotype polymorphism may be a risk factor for CSU.

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“…However, we also found that rs2228570, rs1544410 and rs731236 were not significantly associated with RCC risk, adjusted for covariates. Several previous studies have reported the association between polymorphisms in VDR SNPs and risk of cancer, such as breast cancer and its survivors [20], colorectal cancer [21], lung cancer [22], advanced gallbladder cancer [23], bladder cancer [24], gastric cancer [25] and oral cancer [26]. To date, limited number of studies on relationship between VDR SNPs and RCC risk were performed, in addition, these previous studies could not obtain consistent results.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D receptor gene polymorphisms and its interactions with environmental factors on renal cell carcinoma risk

Jian

Zhang

et al. 2021

Genes and Environ

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Aims We designed a case-control study to investigate the effect of vitamin D receptor gene (VDR) gene single nucleotide polymorphisms (SNPs) and possible gene- environment interaction on the susceptibility of renal cell carcinoma (RCC). Methods Generalized multifactor dimensionality reduction (GMDR) was used to find out the interaction combinations between SNPs and environmental factors, including gene- gene synergy and gene environment synergy effect. Logistic regression was used to analyze the correlation between the four SNPs in VDR gene and RCC, and the significant interaction combinations found by GMDR model were analyzed by hierarchical analysis. Results The genotype distribution of the control group was in accordance with Hardy- Weinberg equilibrium. Logistic regression analysis showed that the risk of RCC in VDR-rs7975232 A allele carriers was significantly higher than that of CC genotype carriers (CA + AA vs. CC), adjusted OR (95 % CI) = 1.75 (1.26–2.28). We used GMDR model to screen the best synergistic model between the four SNPs of VDR gene and smoking and drinking. We found a significant two locus model (P = 0.0010) involving rs7975232 and smoking. The cross- validation consistency of the two- locus model was 10/ 10, and the accuracy was 60.72 %. Compared with non-smokers with rs7975232 -CA or AA genotype, smokers with rs7975232 -CC genotype had the highest risk of RCC, or (95 % CI) = 2.23 (1.42–3.09), after adjustment for covariates. Conclusions We found that the A allele of rs7975232 within VDR gene, interaction between rs7975232 and smoking were all associated with increased RCC risk.

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The role of Vitamin D Receptor gene polymorphisms in colorectal cancer risk

Cited by 5 publications

References 40 publications

The Prognostic Value of the Detection of Microbial Translocation in the Blood of Colorectal Cancer Patients

The Prognostic Value of the Detection of Microbial Translocation in the Blood of Colorectal Cancer Patients

Significant association between Taq1 gene polymorphism in vitamin D receptor and chronic spontaneous urticaria in the Northeast of Iran

Vitamin D receptor gene polymorphisms and its interactions with environmental factors on renal cell carcinoma risk

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