Limits...
Vitamin D Receptor Poly(A) Microsatellite Polymorphism and 25-Hydroxyvitamin D Serum Levels: Association with Susceptibility to Breast Cancer.

Colagar AH, Firouzjah HM, Halalkhor S - J Breast Cancer (2015)

Bottom Line: The vitamin D levels of samples were determined by electrochemiluminescence.A larger increase in the risk for breast cancer was found in individuals with the L carrier genotype and lowered 25(OH)D levels.The results primarily suggest that VDR gene polymorphism in the poly(A) microsatellite is associated with 25(OH)D levels and that it can affect the breast cancer risk in the female population from northern Iran.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Cell Biology, University of Mazandaran Faculty of Basic Sciences, Mazandaran, Iran.

ABSTRACT

Purpose: According to previous studies, vitamin D exhibits protective effects against breast cancer via the vitamin D receptor (VDR). There is growing evidence that breast cancer incidence is associated with various polymorphisms of the VDR gene. This study investigates the association of VDR poly(A) microsatellite variants with 25-hydroxyvitamin D (25(OH)D) serum levels and breast cancer risk.

Methods: Polymorphism analysis was performed on a total of 261 blood samples, which were collected from 134 women with breast cancer and 127 controls. Single strand conformation polymorphism was assessed by polymerase chain reaction in combination with sequencing to detect poly(A) lengths for each sample. The vitamin D levels of samples were determined by electrochemiluminescence.

Results: The poly(A) variant L allele frequency was significantly higher in cancer patients than in controls (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.16-2.57; p=0.006). Thus, carriers of the L allele (LS and LL genotypes) have a higher risk for breast cancer (OR, 1.86; 95% CI, 1.13-3.05; p=0.013). A larger increase in the risk for breast cancer was found in individuals with the L carrier genotype and lowered 25(OH)D levels.

Conclusion: The results primarily suggest that VDR gene polymorphism in the poly(A) microsatellite is associated with 25(OH)D levels and that it can affect the breast cancer risk in the female population from northern Iran.

No MeSH data available.


Related in: MedlinePlus

Genomic structure of the vitamin D receptor (VDR) gene on chromosome 12q13, and locations of single nucleotide polymorphisms (SNPs)on VDR gene. The VDR chromosomal gene containing a total of 11 exon. VDR poly(A) variant is located in 3'-untranslated region.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4490260&req=5

Figure 1: Genomic structure of the vitamin D receptor (VDR) gene on chromosome 12q13, and locations of single nucleotide polymorphisms (SNPs)on VDR gene. The VDR chromosomal gene containing a total of 11 exon. VDR poly(A) variant is located in 3'-untranslated region.

Mentions: Previous preclinical evidence has demonstrated a significant inverse association between 25-hydroxyvitamin D (25(OH)D) serum levels and breast cancer risk [7]. In vitro and in vivo studies have shown apoptotic and antiproliferative effects of vitamin D against various types of cancers, including breast cancer [8]. The active form of vitamin D regulates growth, differentiation and apoptosis that is mediated by the vitamin D receptor (VDR) [9]. VDR is a member of the nuclear receptor family of steroid hormones that acts as transcriptional regulatory factor in most tissues [10]. This protein has an essential role in complex process of proliferation and differentiation of cells by controlling transcription of mediator or target genes [11]. VDR-vitamin D complex, along with the retinoid X receptor family, binds to vitamin D responsive elements in the target genes' promoters to induce or inhibit these genes [12]. A previous animal model study showed enhanced growth and proliferation of breast tissue in VDR knockout mice [13]. The human VDR gene is located on the long arm of chromosome 12 (12q12-14) and includes 11 exons (Figure 1) [14]. There are several single-nucleotide polymorphisms (SNP) on the VDR gene, and breast cancer prevalence is associated with various SNPs of this gene [15]. One of these polymorphisms, a variant length of the poly(A) microsatellite (rs17878969), is located in the 3'-untranslated region of the VDR gene (http://www.ncbi.nlm.nih.gov). According to previous studies, this locus contains a variable number of adenine (A) repeats that lead to different allelic lengths for the locus [1617]. Variety in poly(A) length may affect the VDR gene expression by influencing posttranscriptional regulation [18]. In this study, we determined the length of the poly(A) microsatellite in 134 breast cancer patients and 127 matched controls from northern Iran and examined the relationship between the VDR poly(A) microsatellite length polymorphism and 25(OH)D levels, and how affect breast cancer risk.


Vitamin D Receptor Poly(A) Microsatellite Polymorphism and 25-Hydroxyvitamin D Serum Levels: Association with Susceptibility to Breast Cancer.

Colagar AH, Firouzjah HM, Halalkhor S - J Breast Cancer (2015)

Genomic structure of the vitamin D receptor (VDR) gene on chromosome 12q13, and locations of single nucleotide polymorphisms (SNPs)on VDR gene. The VDR chromosomal gene containing a total of 11 exon. VDR poly(A) variant is located in 3'-untranslated region.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490260&req=5

Figure 1: Genomic structure of the vitamin D receptor (VDR) gene on chromosome 12q13, and locations of single nucleotide polymorphisms (SNPs)on VDR gene. The VDR chromosomal gene containing a total of 11 exon. VDR poly(A) variant is located in 3'-untranslated region.
Mentions: Previous preclinical evidence has demonstrated a significant inverse association between 25-hydroxyvitamin D (25(OH)D) serum levels and breast cancer risk [7]. In vitro and in vivo studies have shown apoptotic and antiproliferative effects of vitamin D against various types of cancers, including breast cancer [8]. The active form of vitamin D regulates growth, differentiation and apoptosis that is mediated by the vitamin D receptor (VDR) [9]. VDR is a member of the nuclear receptor family of steroid hormones that acts as transcriptional regulatory factor in most tissues [10]. This protein has an essential role in complex process of proliferation and differentiation of cells by controlling transcription of mediator or target genes [11]. VDR-vitamin D complex, along with the retinoid X receptor family, binds to vitamin D responsive elements in the target genes' promoters to induce or inhibit these genes [12]. A previous animal model study showed enhanced growth and proliferation of breast tissue in VDR knockout mice [13]. The human VDR gene is located on the long arm of chromosome 12 (12q12-14) and includes 11 exons (Figure 1) [14]. There are several single-nucleotide polymorphisms (SNP) on the VDR gene, and breast cancer prevalence is associated with various SNPs of this gene [15]. One of these polymorphisms, a variant length of the poly(A) microsatellite (rs17878969), is located in the 3'-untranslated region of the VDR gene (http://www.ncbi.nlm.nih.gov). According to previous studies, this locus contains a variable number of adenine (A) repeats that lead to different allelic lengths for the locus [1617]. Variety in poly(A) length may affect the VDR gene expression by influencing posttranscriptional regulation [18]. In this study, we determined the length of the poly(A) microsatellite in 134 breast cancer patients and 127 matched controls from northern Iran and examined the relationship between the VDR poly(A) microsatellite length polymorphism and 25(OH)D levels, and how affect breast cancer risk.

Bottom Line: The vitamin D levels of samples were determined by electrochemiluminescence.A larger increase in the risk for breast cancer was found in individuals with the L carrier genotype and lowered 25(OH)D levels.The results primarily suggest that VDR gene polymorphism in the poly(A) microsatellite is associated with 25(OH)D levels and that it can affect the breast cancer risk in the female population from northern Iran.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Cell Biology, University of Mazandaran Faculty of Basic Sciences, Mazandaran, Iran.

ABSTRACT

Purpose: According to previous studies, vitamin D exhibits protective effects against breast cancer via the vitamin D receptor (VDR). There is growing evidence that breast cancer incidence is associated with various polymorphisms of the VDR gene. This study investigates the association of VDR poly(A) microsatellite variants with 25-hydroxyvitamin D (25(OH)D) serum levels and breast cancer risk.

Methods: Polymorphism analysis was performed on a total of 261 blood samples, which were collected from 134 women with breast cancer and 127 controls. Single strand conformation polymorphism was assessed by polymerase chain reaction in combination with sequencing to detect poly(A) lengths for each sample. The vitamin D levels of samples were determined by electrochemiluminescence.

Results: The poly(A) variant L allele frequency was significantly higher in cancer patients than in controls (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.16-2.57; p=0.006). Thus, carriers of the L allele (LS and LL genotypes) have a higher risk for breast cancer (OR, 1.86; 95% CI, 1.13-3.05; p=0.013). A larger increase in the risk for breast cancer was found in individuals with the L carrier genotype and lowered 25(OH)D levels.

Conclusion: The results primarily suggest that VDR gene polymorphism in the poly(A) microsatellite is associated with 25(OH)D levels and that it can affect the breast cancer risk in the female population from northern Iran.

No MeSH data available.


Related in: MedlinePlus