title: Identification of novel potential genetic predictors of urothelial bladder carcinoma susceptibility in Pakistani population.
abstract: Urothelial bladder carcinoma (UBC) is the most common among urinary bladder neoplasms. We carried out a preliminary study to determine the genetic etiology of UBC in Pakistani population, for this 25 sequence variants from 17 candidate genes were studied in 400 individuals by using polymerase chain reaction-based techniques. Multivariate logistic regression analysis was performed for association analysis of the overall data as well as the data stratified by smoking status, tumor grade and tumor stage. Variants of GSTM1, IGFBP3, LEPR and ACE were found to be associated with altered UBC risk in the overall comparison. CYP1B1 and CDKN1A variants displayed a risk modulation among smokers; IGFBP3 and LEPR variants among non-smokers while GSTM1 polymorphism exhibited association with both. GSTM1 and LEPR variants conferred an altered susceptibility to low grade UBC; GSTT1, IGFBP3 and PPARG variants to high grade UBC while ACE polymorphism to both grades. GSTM1 and LEPR variants exhibited risk modulation for non-muscle-invasive bladder cancer (NMIBC); GSTT1 and PPARG variants for muscle-invasive bladder cancer (MIBC), and ACE variant for NMIBC as well as MIBC. In general, the susceptibility markers were common for low grade and NMIBC; and distinct from those for high grade and MIBC indicating the distinct pathologies of both groups. In brief, our results conform to reports of previously associated variants in addition to identifying novel potential genetic predictors of UBC susceptibility.
authors.affiliation: Department of Biosciences, Faculty of Science, COMSATS Institute of Information Technology, Park Road, Tarlai Kalan, Islamabad, 45600, Pakistan. benishalishah@gmail.com.
authors.forename: Syeda Hafiza Benish
authors.initials: SHB
authors.lastname: Ali
authors.affiliation: Pakistan Atomic Energy Commission General Hospital, Islamabad, 44000, Pakistan.
authors.forename: Kashif Sardar
authors.initials: KS
authors.lastname: Bangash
authors.affiliation: Nishtar Medical College & Hospital, Multan, 60000, Pakistan.
authors.forename: Abdur
authors.initials: A
authors.lastname: Rauf
authors.affiliation: Department of Urology, Mayo Hospital, Lahore, 54000, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Younis
authors.affiliation: Pakistan Atomic Energy Commission General Hospital, Islamabad, 44000, Pakistan.
authors.forename: Khursheed
authors.initials: K
authors.lastname: Anwar
authors.affiliation: Department of Biosciences, Faculty of Science, COMSATS Institute of Information Technology, Park Road, Tarlai Kalan, Islamabad, 45600, Pakistan.
authors.forename: Raja
authors.initials: R
authors.lastname: Khurram
authors.affiliation: Department of Urology, Shifa International Hospital, Islamabad, 44000, Pakistan.
authors.forename: Muhammad Athar
authors.initials: MA
authors.lastname: Khawaja
authors.affiliation: Department of Biosciences, Faculty of Science, COMSATS Institute of Information Technology, Park Road, Tarlai Kalan, Islamabad, 45600, Pakistan.
authors.forename: Maleeha
authors.initials: M
authors.lastname: Azam
authors.affiliation: Department of Radiology, The Children's Hospital & The Institute of Child Health, Lahore, 54000, Pakistan.
authors.forename: Abid Ali
authors.initials: AA
authors.lastname: Qureshi
authors.affiliation: Department of Urology, Shifa International Hospital, Islamabad, 44000, Pakistan.
authors.forename: Saeed
authors.initials: S
authors.lastname: Akhter
authors.affiliation: Department for Health Evidence and Department of Urology, Radboud University Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Lambertus A
authors.initials: LA
authors.lastname: Kiemeney
authors.affiliation: Department of Biosciences, Faculty of Science, COMSATS Institute of Information Technology, Park Road, Tarlai Kalan, Islamabad, 45600, Pakistan. raheelqamar@hotmail.com.|Al-Nafees Medical College & Hospital Isra University, Islamabad, 45600, Pakistan. raheelqamar@hotmail.com.|Pakistan Academy of Sciences, Islamabad, 44000, Pakistan. raheelqamar@hotmail.com.
authors.forename: Raheel
authors.initials: R
authors.lastname: Qamar
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics; D010154:Pakistan; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D054411:Receptors, Leptin / Q000235:genetics; D012907:Smoking; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D065633:Cytochrome P-450 CYP1B1; D005982:Glutathione Transferase; D018972:Insulin-Like Growth Factor Binding Protein 3; D047495:PPAR gamma; D007703:Peptidyl-Dipeptidase A; D054411:Receptors, Leptin; C515497:IGFBP3 protein, human; C515448:LEPR protein, human; C585496:CYP1B1 protein, human; C488034:ACE protein, human
keywords: Cancer; Genetic association study; Genetic polymorphisms; Genetic predictors; Pakistan; Urothelial bladder carcinoma