Functional POR A503V is associated with the risk of bladder cancer in a Chinese population

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...

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Published inScientific reports Vol. 5; no. 1; p. 11751
Main Authors Xiao, Xue, Ma, Gaoxiang, Li, Shushu, Wang, Meilin, Liu, Nian, Ma, Lan, Zhang, Zhan, Chu, Haiyan, Zhang, Zhengdong, Wang, Shou-Lin
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 30.06.2015
Nature Publishing Group
Subjects
38/23
38/70
692/53/2423
692/699/67/589/1336
82/80
Aged
Animals
Bladder cancer
Cancer
Carcinogens
Case-Control Studies
China
CHO Cells
Colonies
Cricetinae
Cricetulus
Cytochrome
Cytochrome c
Cytochrome P-450 Enzyme System - genetics
Cytochrome P450
Exons
Female
Gene Frequency
Genetic Association Studies
Genetic Predisposition to Disease
Geriatrics
Health risk assessment
Hormones
Humanities and Social Sciences
Humans
Invasiveness
Male
Middle Aged
Mitomycin C
multidisciplinary
Mutation, Missense
Oxidoreductase
Polymorphism, Single Nucleotide
Protective Factors
Risk Factors
Science
Sequence Analysis, DNA
Smoking
Urinary bladder
Urinary Bladder Neoplasms - genetics
China
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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.
AbstractList 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.
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.
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.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.
ArticleNumber 11751
Author Ma, Lan
Zhang, Zhengdong
Wang, Shou-Lin
Ma, Gaoxiang
Xiao, Xue
Liu, Nian
Wang, Meilin
Zhang, Zhan
Li, Shushu
Chu, Haiyan
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Snippet Human cytochrome P450 oxidoreductase (POR) plays important roles in the metabolism of exogenous carcinogens and endogenous sterol hormones. However, few...
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StartPage 11751
SubjectTerms 38/23
38/70
692/53/2423
692/699/67/589/1336
82/80
Aged
Animals
Bladder cancer
Cancer
Carcinogens
Case-Control Studies
China
CHO Cells
Colonies
Cricetinae
Cricetulus
Cytochrome
Cytochrome c
Cytochrome P-450 Enzyme System - genetics
Cytochrome P450
Exons
Female
Gene Frequency
Genetic Association Studies
Genetic Predisposition to Disease
Geriatrics
Health risk assessment
Hormones
Humanities and Social Sciences
Humans
Invasiveness
Male
Middle Aged
Mitomycin C
multidisciplinary
Mutation, Missense
Oxidoreductase
Polymorphism, Single Nucleotide
Protective Factors
Risk Factors
Science
Sequence Analysis, DNA
Smoking
Urinary bladder
Urinary Bladder Neoplasms - genetics
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Title Functional POR A503V is associated with the risk of bladder cancer in a Chinese population
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