The Polymorphism in the Caudal-Related Homeodomain Protein Cdx-2 Binding Element in the Human Vitamin D Receptor Gene

Arai, Hidekazu; Miyamoto, Ken‐ichi; Yoshida, Michiko; Yamamoto, Hironori; Taketani, Yutaka; Morita, Kyoko; Kubota, Megumi; Yoshida, Shu; Ikeda, Mikiko; Watabe, Fumiko; Kanemasa, Yasuhiro; Takeda, Eiji

doi:10.1359/jbmr.2001.16.7.1256

Cited by 242 publications

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“…Polymorphism effect is dependent on its location within the VDR gene. Cdx2 polymorphism in VDR promoter modify VDR intestinal transcription and regulation of calcium absorption (Arai et al, 2001). Polymorphism in 3` VDR gene regulatory region within Bsm1, Apa1, and Taq1, are involved in VDR gene regulation and mRNA stability (Richetta et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Association between Circulating Vitamin D, the Taq1 Vitamin D Receptor Gene Polymorphism and Colorectal Cancer Risk among Jordanians

Atoum¹,

Tchoporyan²

2014

Asian Pacific Journal of Cancer Prevention

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Section: Introductionmentioning

confidence: 99%

Association between Circulating Vitamin D, the Taq1 Vitamin D Receptor Gene Polymorphism and Colorectal Cancer Risk among Jordanians

Atoum¹,

Tchoporyan²

2014

Asian Pacific Journal of Cancer Prevention

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“…27 The VDR Cdx2 G>A promoter variant maps to a binding site for an intestinalspecific transcription factor and confers altered transcriptional activity. 28 The FokI translational start codon polymorphism has structural consequences for the VDR which result in a less transcriptionally potent protein. 29,30 In addition, 2 intronic polymorphisms, BsmI and ApaI, and the TaqI polymorphism in exon 9 have been reported to alter VDR expression, probably through linkage disequilibrium with variants in the 3 0 UTR altering VDR-mRNA stability.…”

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confidence: 99%

Dairy products, polymorphisms in the vitamin D receptor gene and colorectal adenoma recurrence

Muir

Liu

Logan

et al. 2008

Intl Journal of Cancer

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Vitamin D receptor (VDR) activation inhibits proliferation and angiogenesis in the colorectal epithelium, and inhibits metastasis of colorectal tumors. Polymorphisms in the VDR gene alter receptor cellular levels and functioning, and may confer altered susceptibility to colorectal neoplasia. We aimed to investigate the influence of VDR polymorphisms and dietary factors impacting on vitamin D metabolism on colorectal adenoma (CRA) recurrence. Data on dietary intakes of calcium, vitamin D and dairy products were collected from 853 participants in the United Kingdom Colorectal Adenoma Prevention trial, a randomized trial of aspirin and folate for CRA recurrence prevention. The VDR Cdx2, FokI, BsmI, ApaI and TaqI polymorphisms were genotyped in 546 participants with available DNA, and gene-diet interaction analyses performed in 480. Dairy product intake was inversely related to CRA recurrence risk independent of calcium and vitamin D [relative risk (RR) 5 0.64; 95% confidence intervals (CIs): 0.47-0.88, for subjects in the highest compared to lowest intake tertile, p trend 5 0.005]. Milk accounted for 60% of dairy product intake, and on analysis of milk and nonmilk dairy products separately recurrence risk in individuals in the highest tertile of milk intake was half that of lowest tertile individuals (RR 5 0.52; 95% CI: 0.38-0.72, p trend 5 3.2 3 10 25 ), whereas nonmilk dairy products did not influence recurrence. VDR polymorphism genotypes and haplotypes did not directly alter recurrence risk, but the reduction in risk associated with high dairy product intake was confined to individuals with ApaI aA/AA genotype (p interaction 5 0.02). These findings indicate dairy products, and in particular milk, have chemopreventive activity against CRA recurrence. ' 2008 Wiley-Liss, Inc.Key words: colorectal adenoma recurrence; dairy products; VDR; polymorphism Colorectal cancer (CRC) is the third commonest cancer worldwide after lung and breast cancer, and two-thirds of CRC occurs in developed countries. 1 Up to 90% of CRCs develop from colorectal adenomas (CRAs) and colonoscopic removal of CRA reduces the incidence of CRC. 2,3 In some individuals, the recurrence rate for CRA is as high as 40-50% after 3 years, 4 CRA recurrence is a surrogate marker for CRC risk and prevention of CRA recurrence is a useful endpoint for evaluating chemopreventive agents. 5 Activation of vitamin D receptors (VDRs) present in many cell types, including colorectal epithelial cells, can inhibit proliferation, angiogenesis and invasiveness, and studies in animal models indicate that vitamin D supplementation can lower the incidence and metastatic potential of intestinal tumors. 6-9 Ecological studies correlating sunlight exposure with cancer incidence provided the first evidence that vitamin D levels are inversely related to CRC development in humans. 10 Subsequent epidemiological studies have reported lower risks of CRA and CRC in individuals with high intakes and circulating levels of vitamin D. 11-14 Vitamin D plays a crucial role in calcium me...

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“…The 3 0 polymorphisms are Apa 1 (Faraco et al, 1989) and Bsm 1 (Morrison et al, 1992) in intron 8, Taq 1 (Morrison et al, 1992) in a silent site in exon 9 and a length polymorphism of a polyadenyl (polyA) microsatellite in the 3 0 -untranslated region (Ingles et al, 1997b), classified into long (L) and short (S) variants (L demonstrates linkage disequilibrium with b, a, T). The 5 0 polymorphisms are Fok 1 (Saijo et al, 1991) situated in exon 2, 10 base pairs upstream from an ATG translation start point, and a recently described polymorphism in the promoter region, situated at À3731 bp relative to the exon 1a transcription start site (Arai et al, 2001) within a binding element of Cdx-2, which is a caudalrelated homeodomain transcription factor. The 3 0 region polymorphisms do not affect VDR protein structure, while Fok 1 (C -T transition) alters an ACG codon resulting in a further upstream start codon and a three amino-acid extended protein (Saijo et al, 1991).…”

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“…The expression of Cdx-2 has also been found in other tissues such as the brain and prostate. Polymorphism at the Cdx-2-binding site significantly alters the transcriptional activity of the VDR promoter region (Arai et al, 2001).…”

mentioning

confidence: 99%

A novel polymorphism in the 1A promoter region of the vitamin D receptor is associated with altered susceptibilty and prognosis in malignant melanoma

et al. 2004

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The association of Taq 1 and Fok 1 restriction fragment length polymorphisms of the vitamin D receptor with occurrence and outcome of malignant melanoma (MM), as predicted by tumour (Breslow) thickness, has been reported previously. We now report a novel adenine -guanine substitution À1012 bp relative to the exon 1a transcription start site (A-1012G), found following screening by single-stranded conformational polymorphism of this promoter region. There was a total of 191 MM cases , which were stratified according to conventional Breslow thickness groups, cases being randomly selected from each group to form a distribution corresponding to the known distribution of Breslow thickness in our area, and this population (n ¼ 176) was compared to 80 controls. The A allele was over-represented in MM patients and, with GG as reference, odds ratio (OR) for AG was 2.5, 95% confidence interval (CI) 1.1 -5.7, (P ¼ 0.03) and AA 3.3, CI 1.4 -8.1, (P ¼ 0.007). The outcome was known in 171 of 191 patients and the A allele was related to the development of metastasis, the Kaplan -Meier estimates of the probability of metastasis at 5 years being: GG 0%; AG 9%, CI 4 -16%; AA 21%, CI 12 -36%; (P ¼ 0.008), and to thicker Breslow thickness groups (P ¼ 0.04). The effect on metastasis was independent of tumour thickness and A-1012G may have predictive potential, additional to Breslow thickness. Neither the Fok 1 nor Taq 1 variants (f and t) were significantly related to the development of metastasis, although there was a strong relationship of fftt with the thickest Breslow thickness group (P ¼ 0.005). There was an interaction between the A-1012G and Fok 1 polymorphisms (P ¼ 0.025) and the Fok 1 variant enhanced the effect of the A allele of the A-1012G polymorphism on metastasis, the probability of metastasis for AAff at 5 years follow-up being 57%, CI 24 -92%.

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The Polymorphism in the Caudal-Related Homeodomain Protein Cdx-2 Binding Element in the Human Vitamin D Receptor Gene

Abstract: ABSTRACT

Cited by 242 publications

References 45 publications

Association between Circulating Vitamin D, the Taq1 Vitamin D Receptor Gene Polymorphism and Colorectal Cancer Risk among Jordanians

Association between Circulating Vitamin D, the Taq1 Vitamin D Receptor Gene Polymorphism and Colorectal Cancer Risk among Jordanians

Dairy products, polymorphisms in the vitamin D receptor gene and colorectal adenoma recurrence

A novel polymorphism in the 1A promoter region of the vitamin D receptor is associated with altered susceptibilty and prognosis in malignant melanoma

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