J Breast Cancer.  2015 Jun;18(2):119-125. 10.4048/jbc.2015.18.2.119.

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

• Colagar AH
• Firouzjah
• Halalkhor

• KMID: 2374526
• DOI: http://doi.org/10.4048/jbc.2015.18.2.119

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.

Keyword

25-Hydroxyvitamin D 2; Breast neoplasms; Calcitriol receptors; Genetic polymorphism; Microsatellite repeats

MeSH Terms

25-Hydroxyvitamin D 2
Alleles
Breast Neoplasms*
Female
Gene Frequency
Genotype
Humans
Incidence
Iran
Microsatellite Repeats*
Polymerase Chain Reaction
Polymorphism, Genetic
Receptors, Calcitriol*
Vitamin D
25-Hydroxyvitamin D 2
Receptors, Calcitriol
Vitamin D

Figure

• 

  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.

• 

  Figure 2 Polymerase chain reaction product in nondenaturing polyacrylamide gel electrophoresis, visualized by silver nitrate staining: SS genotype with ~236-238 bp and LL genotype with ~241-243 bp.

• 

  Figure 3 Single-strand conformation polymorphism (SSCP) results of the polymerase chain reaction (PCR) product in denaturing polyacrylamide gel electrophoresis, visualized by silver nitrate staining: (A) PCR products of the SS genotype with ~236-238 bp and LL genotype with ~241-243 bp in SSCP gel; (B) Schematic of the adenine numeric repeat shown by number in single strand oligonucleotide bands or different alleles.

• 

  Figure 4 Deoxyribonucleic acid electropherogram analysis of poly(A) repeat polymorphism in the 3'-untranslated region of vitamin D receptor gene regions: S and L alleles with poly(A)-microsatellite A-repeats 14-16 and 19-21, respectively.

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