title: Combined Genetic Biomarkers Confer Susceptibility to Risk of Urothelial Bladder Carcinoma in a Saudi Population.
abstract: We evaluated the associations between seven single nucleotide polymorphisms and susceptibility to urothelial bladder carcinoma (UBC) in a Saudi population. Genomic DNA was taken from buccal cells of 52 patients with UBC and 104 controls for genotyping of GSTT1, GSTM1, rs4646903, rs1048943, TP53 rs1042522, rs1801133, and rs1801394 using PCR and TaqMan® assays. The rs1801133 and rs1801394 variants showed strong associations with UBC (OR = 2.3,P= 0.0002; OR = 2.6,P= 0.0001, resp.). Homozygosity of Pro72 conferred a significant double risk in cases compared with controls (30.8% versus 15.4%), but the homozygote Arg/Arg had no effect on risk. Genotypic combinations of GSTM1/GSTT1, rs4646903/rs1048943, and rs1801133/rs1801394 exhibited significant linkage with the disease (χ2= 10.3,P= 0.006;χ2= 13.9,P= 0.003; andχ2= 20.4,P= 0.0004, resp.). The GSTM1 and rs1042522Arg and rs1801394G variant alleles were more frequent in current smokers with UBC (52.4%, 52.5%, and 64.3%, resp.) than were the corresponding wild-types. Despite some variants having only a slight effect on UBC risk, the interaction effect of combined genetic biomarkers-or even the presence of one copy of a variant allele-is potentially much greater. Perhaps more studies regarding next-generation genetic sequencing and its utility can add to the risk of UBC.
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, P.O. Box 57543, Mecca 21955, Saudi Arabia; Department of Molecular Genetics, Medical Genetics Center, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt.
authors.forename: Nasser Attia
authors.identifier: 0000-0002-9137-351X
authors.initials: NA
authors.lastname: Elhawary
authors.affiliation: Department of Surgery, Faculty of Medicine, Umm Al-Qura University, Mecca 21955, Saudi Arabia; Department of Urology, King Abdullah Medical City Specialist Hospital, Mecca 21955, Saudi Arabia.
authors.forename: Anmar
authors.initials: A
authors.lastname: Nassir
authors.affiliation: Department of Urology, King Abdullah Medical City Specialist Hospital, Mecca 21955, Saudi Arabia.
authors.forename: Hesham
authors.initials: H
authors.lastname: Saada
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, P.O. Box 57543, Mecca 21955, Saudi Arabia.
authors.forename: Anas
authors.initials: A
authors.lastname: Dannoun
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, P.O. Box 57543, Mecca 21955, Saudi Arabia.
authors.forename: Omar
authors.initials: O
authors.lastname: Qoqandi
authors.affiliation: Division of Internal Medicine, Al-Noor Specialist Hospital, Mecca 21955, Saudi Arabia.
authors.forename: Ammar
authors.initials: A
authors.lastname: Alsharif
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, P.O. Box 57543, Mecca 21955, Saudi Arabia.
authors.forename: Mohammed Taher
authors.initials: MT
authors.lastname: Tayeb
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012529:Saudi Arabia; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D005982:Glutathione Transferase; D016159:Tumor Suppressor Protein p53; C495901:TP53 protein, human; C413545:glutathione S-transferase T1