Functional POR A503V is associated with the risk of bladder cancer in a Chinese population.
Functional POR A503V is associated with the risk of bladder cancer in a Chinese population.
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功能性 POR A503V 与中国人群患膀胱癌的风险相关
DOI：
10.1038/srep11751
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发表时间：
2015-06-30
影响因子：
4.6
通讯作者：
Wang SL
中科院分区：
文献类型：
--
作者：
Xiao X;Ma G;Li S;Wang M;Liu N;Ma L;Zhang Z;Chu H;Zhang Z;Wang SL
人细胞色素P450氧化还原酶（POR）在外源性致癌物和内源性固醇激素的代谢中发挥重要作用。然而，很少有研究探讨POR变异与膀胱癌风险之间的关联。在这项研究中，我们首先对随机选择的50名对照中的所有16个POR外显子进行测序，发现了三种变异，rs 1135612，rs 1057868（A503 V）和rs 2228104，然后在中国人群中对1，050例膀胱癌病例和1，404例无癌对照进行病例对照研究，评估其与膀胱癌风险的关系。在隐性模型中，A503 V TT基因型的人患膀胱癌的风险降低（TTvs. CC/CT，OR = 0.73，95%CI = 0.57-0.93），这在老年男性、不吸烟受试者中更为明显。尤其是A503 V TT基因型在肿瘤浸润期表现出保护作用。功能分析显示，A503 V活性在细胞色素还原中降低（50.5单位/mgvs. 135.4单位/mg）、丝裂霉素C清除率（38.3%vs.96.8%）和丝裂霉素C诱导的集落形成率（78.0vs.34.3个/皿）。结果提示，POR A503 V可能通过降低其代谢活性而降低膀胱癌发病风险，有望成为预测膀胱癌易感性的潜在生物标志物。
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 16PORexons 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 (TTvs. 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 cytochromecreduction (50.5 units/mgvs. 135.4 units/mg), mitomycin C clearance (38.3%vs. 96.8%) and mitomycin C-induced colony formation (78.0vs34.3 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.
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影响因子：
30.8
作者：
通讯作者：
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影响因子：
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作者：
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