Association of FokI polymorphism of vitamin D receptor with urothelial bladder cancer in Tunisians: role of tobacco smoking and plasma vitamin D concentration

Mohamed Kacem Ben Fradj, Amani Kallel, Mohamed Mourad Gargouri, Mohamed Ali Ben Chehida, Ahmed Sallemi, Yassine Ouanes, Sami Ben Rhouma, Jemaa Riadh, Moncef Feki, Yassine Nouira, Naziha Kaabachi

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.