title: Vitamin D receptor FokI and BsmI gene polymorphism and its association with grade and stage of renal cell carcinoma in North Indian population.
abstract: Vitamin D exerts its activity through binding to the high-affinity nuclear vitamin D receptor (VDR), and majority of genetic studies have primarily focused on variation within this gene. Therefore, analysis of genetic variation in VDR genes may provide insight into the role of vitamin D in renal cell carcinoma (RCC) etiology in our study population. This study investigated whether VDR gene polymorphisms were associated with increased risk and prognosis of RCC in the North Indian population. Genotyping of two polymorphic sites (FokI and BsmI) in the VDR gene of 196 RCC cases and 250 healthy controls was performed via PCR-RFLP. The frequency of homozygous genotype FF was 31.6%, heterozygous Ff was 48.0%, and homozygous ff was 20.4% in cases, whereas in controls it was 45.6%, 39.2%, and 15.2%, respectively; thus, there was a significant difference between the two groups (p (Trend) = 0.011) in the univariate model. The frequencies of the BB, Bb, and bb genotypes were 25.5%, 44.9% and 29.6% in cases, respectively, while in controls it was 33.2%, 52.0% and 14.8%, respectively; thus, there was a significant difference between the two groups (p (Trend) = 0.001) in the univariate model. The two high-risk genotype ff of FokI and bb of BsmI of VDR showed a cumulative 1.87-fold increase in risk to RCC. Moreover, the FF genotype was associated with lower pathological stage and histological grade. Our results suggest that the FokI and BsmI genotypes of VDR gene may be implicated in the pathogenesis of RCC.
authors.affiliation: Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard, Hamdard University, Hamdard Nagar, New Delhi 110062, India.
authors.forename: Wani
authors.initials: W
authors.lastname: Arjumand
authors.forename: Shiekh Tanveer
authors.initials: ST
authors.lastname: Ahmad
authors.forename: Amlesh
authors.initials: A
authors.lastname: Seth
authors.forename: Ashish Kumar
authors.initials: AK
authors.lastname: Saini
authors.forename: Sarwat
authors.initials: S
authors.lastname: Sultana
mesh_terms: D054458:Amplified Fragment Length Polymorphism Analysis; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology*; D015252:Deoxyribonucleases, Type II Site-Specific; D005260:Female; D006360:Heat-Shock Proteins; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D010446:Peptide Fragments; D012150:Polymorphism, Restriction Fragment Length; D018167:Receptors, Calcitriol / Q000235:genetics*
chemical_list: D006360:Heat-Shock Proteins; D010446:Peptide Fragments; D018167:Receptors, Calcitriol; C063820:SNP nonapeptide; C053864:endodeoxyribonuclease BsmI; C035042:endodeoxyribonuclease FokI; D015252:Deoxyribonucleases, Type II Site-Specific