title: Vitamin D receptor Cdx-2 polymorphism and premenopausal breast cancer risk in southern Pakistani patients.
abstract: BACKGROUND
  Vitamin D3 is a secoster oid that exerts its effect by binding to its nuclear receptor called vitamin D receptor (VDR), inducing apoptosis and thereby inhibiting cell proliferation in cancer cells. The VDR receptor, located in the nucleus, is known to regulate the functions of over 200 genes. Various allelic forms of hVDR have been discovered that increase susceptibility to various cancers. The VDR-Cdx2 polymorphism, located in the promoter region of exon 1e in the VDR gene, influences the functional activity of the receptor, since the hVDR lacks consensus TATA and CAAT boxes. The current investigation examines the association between VDR-Cdx2 polymorphism and breast cancer in premenopausal females from Southern Pakistan.
  
  
  METHODS
  We conducted a case control study on 264 subjects (103 cases and 161 controls) who were recruited from a tertiary hospital located in Karachi, Pakistan. Genomic DNA was extracted from peripheral blood using a commercial kit method, and the VDR-Cdx2 polymorphism was genotyped using tetraprimer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR) method. Pearson chi square test was used to assess the association between VDR-Cdx2 genotype and breast cancer while genotype distribution in controls was evaluated by Hardy-Weinberg equilibrium (HWE). Breast cancer risk was calculated using odds ratios and 95% confidence intervals.
  
  
  RESULTS
  The genotype distribution in the control group was in HWE (p > 0.05) for the VDR-Cdx2 polymorphism. A non-significant association was observed between VDR cdx2 polymorphism and breast cancer, however the GG genotype was at risk (OR = 1.832, 95% CI = 0.695-4.828) of developing breast cancer.
  
  
  CONCLUSIONS
  The GG genotype of Cdx2-VDR gene polymorphism may increase the risk of developing breast cancer in young female patients in South Pakistan. Further investigations examining additional single nucleotide polymorphisms (SNPs) in VDR are required to assess their relationships with breast cancer.
authors: Department of Physiology, University of Karachi, Karachi, Pakistan.
authors: Mehr un Nisa
authors: Mu
authors: Iqbal
authors: Department of Physiology, University of Karachi, Karachi, Pakistan.
authors: Taseer Ahmed
authors: TA
authors: Khan
authors: Department of Clinical Oncology, Karachi Institute of Radiotherapy and Nuclear Medicine, Karachi, Pakistan.
authors: Syed Amir
authors: SA
authors: Maqbool
mesh_terms: D000328:Adult; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D000071616:CDX2 Transcription Factor; D016022:Case-Control Studies; D015331:Cohort Studies; D004247:DNA / Q000032:analysis / Q000302:isolation & purification; D005260:Female; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D016017:Odds Ratio; D010154:Pakistan; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D017697:Premenopause; D011401:Promoter Regions, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics*; D012189:Retrospective Studies; D012306:Risk; D062606:Tertiary Care Centers
chemical_list: D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; D018167:Receptors, Calcitriol; D004247:DNA