title: Functional POR A503V is associated with the risk of bladder cancer in a Chinese population.
abstract: Human cytochrome P450 oxidoreductase (POR) plays important roles in the metabolism of exogenous carcinogens and endogenous sterol hormones. However, few studies have explored the association between POR variants and the risk of bladder cancer. In this study, we first sequenced all 16 POR exons among 50 randomly selected controls, and found three variants, rs1135612, rs1057868 (A503V) and rs2228104, which were then assessed the relation to risk of bladder cancer in a case-control study of 1,050 bladder cancer cases and 1,404 cancer-free controls in a Chinese population. People with A503V TT genotype have a decreased risk of bladder cancer in a recessive model (TT vs. CC/CT, OR = 0.73, 95% CI = 0.57-0.93), which was more pronounced among elderly male, non-smoking, subjects. Especially, A503V TT genotype showed a protective effect in the invasive tumor stage. Functional analysis revealed that A503V activity decreased in cytochrome c reduction (50.5 units/mg vs. 135.4 units/mg), mitomycin C clearance (38.3% vs. 96.8%), and mitomycin C-induced colony formation (78.0 vs 34.3 colonies per dish). The results suggested that POR A503V might decrease the risk of bladder cancer by reducing its metabolic activity, and should be a potential biomarker for predicting the susceptibility to human bladder cancer.
authors.affiliation: 1] Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue Nanjing 211166, P. R. China [2] State Key Lab of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 140 Hanzhong Rd., Nanjing 210029, P. R. China.
authors.forename: Xue
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue Nanjing 211166, P. R. China.
authors.forename: Gaoxiang
authors.initials: G
authors.lastname: Ma
authors.affiliation: 1] Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue Nanjing 211166, P. R. China [2] State Key Lab of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 140 Hanzhong Rd., Nanjing 210029, P. R. China.
authors.forename: Shushu
authors.initials: S
authors.lastname: Li
authors.affiliation: Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue Nanjing 211166, P. R. China.
authors.forename: Meilin
authors.initials: M
authors.lastname: Wang
authors.affiliation: 1] Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue Nanjing 211166, P. R. China [2] State Key Lab of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 140 Hanzhong Rd., Nanjing 210029, P. R. China.
authors.forename: Nian
authors.initials: N
authors.lastname: Liu
authors.affiliation: Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue Nanjing 211166, P. R. China.
authors.forename: Lan
authors.initials: L
authors.lastname: Ma
authors.affiliation: 1] Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue Nanjing 211166, P. R. China [2] State Key Lab of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 140 Hanzhong Rd., Nanjing 210029, P. R. China.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue Nanjing 211166, P. R. China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Chu
authors.affiliation: Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue Nanjing 211166, P. R. China.
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: 1] Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue Nanjing 211166, P. R. China [2] State Key Lab of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 140 Hanzhong Rd., Nanjing 210029, P. R. China.
authors.forename: Shou-Lin
authors.initials: SL
authors.lastname: Wang
mesh_terms: D000368:Aged; D000818:Animals; D016466:CHO Cells; D016022:Case-Control Studies; D002681:China; D006224:Cricetinae; D003412:Cricetulus; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D065840:Protective Factors; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
chemical_list: C000602470:POR protein, human; D003577:Cytochrome P-450 Enzyme System