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  • Alternation of genome can change the cellular phenotype to evolve from a preneoplastic stage into cancer [pone.0082804-Thorgeirsson1]. It is clear that genetics play an important role in carcinogenesis. SNP may influence gene expression, messenger RNA stability and subcellular localization of mRNAs and/or proteins to produce disease [pone.0082804-Shastry1]. CA9 SNP patients with metastatic clear cell renal cell carcinoma may be associated with better survival and a greater opportunity to response to interleukin-2 [pone.0082804-deMartino1]. It is also reported that CA9 gene polymorphisms, smoking and betel-quid chewing might alter oral cancer susceptibility and metastasis [pone.0082804-Chien1]. Increasing evidences suggest gene polymorphism is associated with the risk and progression of UCC [pone.0082804-Wu2] and can be considered as a prognostic factor of chemoradiotherapy [pone.0082804-Sakano1]. Cigarette smoking is the most important risk factor for bladder cancer [pone.0082804-Zeegers1]. The present study showed patients with the rs1048638 (3’-UTR regions of the CA9 gene) polymorphism had increased risk of UCC and invasive cancer stage ([pone-0082804-t002] and [pone-0082804-t003]). Smoking can increase the risk of invasive cancer in the CA9 SNP UCC patients ([pone-0082804-t004]). These lines of evidence suggest that genetic factor and environmental carcinogen exposure were involved in the formation or pathogenesis of UCC.

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