title: Association of FokI polymorphism of vitamin D receptor with urothelial bladder cancer in Tunisians: role of tobacco smoking and plasma vitamin D concentration.
abstract: The aim of the study was to test whether the VDR FokI polymorphism is associated with the risk of urothelial bladder cancer (UBC) in Tunisians. The study included 200 unrelated patients with UBC and 200 healthy controls. Genotyping of the VDR FokI polymorphism was determined by PCR-RFLP method. Plasma 25-hydroxyvitamin D concentrations were measured by immunoassay. Binary logistic regression model was applied to test how the association of VDR FokI polymorphism is independent of potential confounding factors. Genotype distribution (FF, 45 vs. 55 %; Ff, 52.1 vs. 47.9 %, and ff, 12 vs. 5.5 %, respectively) and allele frequencies (F, 66.5 vs. 74.8 % and f, 33.5 vs. 25.2 %, respectively) were significantly different between UBC patients and controls. The "ff" genotype [OR (95 % CI), 2.66 (1.24-5.73); p = 0.012] and "f" allele [1.49 (1.09-2.02); p = 0.010] were associated with increased risk of UBC. The association remained significant in multivariate analysis. Stratified analyses showed that VDR FokI polymorphism is only associated with UBC risk in ever-smokers, subjects exposed to chemical carcinogens and those with plasma 25-hydroxyvitamin D over 12 μg/L. The "f" allele of VDR FokI polymorphism is associated with a higher risk of UBC in Tunisians, especially in smokers as well as subjects with occupational exposition and subjects without vitamin D deficiency. These results should be replicated in other ethnic groups and the influence of other genetic factors and environments on this association should be investigated.
authors.affiliation: Faculty of Medicine of Tunis, UR05/08-08, LR99ES11, Department of Biochemistry, Rabta Hospital, University Tunis El Manar, 1007, Jebbari, Tunis, Tunisia. kacim1984@hotmail.fr.|Laboratory of Biochemistry, Rabta Hospital, 1007, Jebbari, Tunis, Tunisia. kacim1984@hotmail.fr.|Faculty of Sciences of Tunis, University Tunis El Manar, Campus Universitaire, 2092, Tunis, Tunisia. kacim1984@hotmail.fr.
authors.forename: Mohamed Kacem
authors.initials: MK
authors.lastname: Ben Fradj
authors.affiliation: Faculty of Medicine of Tunis, UR05/08-08, LR99ES11, Department of Biochemistry, Rabta Hospital, University Tunis El Manar, 1007, Jebbari, Tunis, Tunisia.
authors.forename: Amani
authors.initials: A
authors.lastname: Kallel
authors.affiliation: Faculty of Medicine of Tunis, UR12SP04, Department of Urology, Rabta Hospital, University Tunis El Manar, 1007, Jebbari, Tunis, Tunisia.
authors.forename: Mohamed Mourad
authors.initials: MM
authors.lastname: Gargouri
authors.affiliation: Faculty of Medicine of Tunis, UR12SP04, Department of Urology, Rabta Hospital, University Tunis El Manar, 1007, Jebbari, Tunis, Tunisia.
authors.forename: Mohamed Ali Ben
authors.initials: MA
authors.lastname: Chehida
authors.affiliation: Faculty of Medicine of Tunis, UR12SP04, Department of Urology, Rabta Hospital, University Tunis El Manar, 1007, Jebbari, Tunis, Tunisia.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Sallemi
authors.affiliation: Faculty of Medicine of Tunis, UR12SP04, Department of Urology, Rabta Hospital, University Tunis El Manar, 1007, Jebbari, Tunis, Tunisia.
authors.forename: Yassine
authors.initials: Y
authors.lastname: Ouanes
authors.affiliation: Faculty of Medicine of Tunis, UR12SP04, Department of Urology, Rabta Hospital, University Tunis El Manar, 1007, Jebbari, Tunis, Tunisia.
authors.forename: Sami Ben
authors.initials: SB
authors.lastname: Rhouma
authors.affiliation: Faculty of Medicine of Tunis, UR05/08-08, LR99ES11, Department of Biochemistry, Rabta Hospital, University Tunis El Manar, 1007, Jebbari, Tunis, Tunisia.
authors.forename: Jemaa
authors.initials: J
authors.lastname: Riadh
authors.affiliation: Faculty of Medicine of Tunis, UR05/08-08, LR99ES11, Department of Biochemistry, Rabta Hospital, University Tunis El Manar, 1007, Jebbari, Tunis, Tunisia.
authors.forename: Moncef
authors.initials: M
authors.lastname: Feki
authors.affiliation: Faculty of Medicine of Tunis, UR12SP04, Department of Urology, Rabta Hospital, University Tunis El Manar, 1007, Jebbari, Tunis, Tunisia.
authors.forename: Yassine
authors.initials: Y
authors.lastname: Nouira
authors.affiliation: Faculty of Medicine of Tunis, UR05/08-08, LR99ES11, Department of Biochemistry, Rabta Hospital, University Tunis El Manar, 1007, Jebbari, Tunis, Tunisia.
authors.forename: Naziha
authors.initials: N
authors.lastname: Kaabachi
mesh_terms: D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016017:Odds Ratio; D012150:Polymorphism, Restriction Fragment Length; D018167:Receptors, Calcitriol / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects; D014416:Tunisia; D001749:Urinary Bladder Neoplasms / Q000097:blood / Q000209:etiology* / Q000473:pathology; D014807:Vitamin D / Q000097:blood
chemical_list: D018167:Receptors, Calcitriol; D014807:Vitamin D
keywords: FokI; Plasma vitamin D concentration; Tobacco smoking; Urothelial bladder cancer; VDR gene