title: EGFR 3'UTR 774T>C polymorphism contributes to bladder cancer risk.
abstract: Much evidence show that over-expression of epidermal growth factor receptor (EGFR) plays an important role in regulating carcinogenesis. Genetic variations in 3' untranslated region (3'UTR) of gene have been reported to affect gene expression by interfering with microRNAs (miRNAs), which are thought to function as either tumour suppressors or oncogenes by binding to their target mRNA. In this study, we investigated the association between the EGFR 3'UTR 774T>C polymorphism and bladder cancer risk. We used the TaqMan technology to genotype this genetic variant in a hospital-based case-control study of 908 bladder cancer patients and 1239 controls in a Chinese population. We found that the 774CC genotype was associated with a statistically significantly increased risk of bladder cancer [adjusted odds ratio = 1.29, 95% confidence interval = 1.05-1.58], compared with the 774TT/TC genotype, and this increased risk was more pronounced among subgroups of age > 65 years, non-smokers and patients' tumour invasive stage. Furthermore, luciferase assays in T24 cell showed that EGFR 3'UTR 774 T to C substitution could increase the expression of EGFR, which was consistent with the association study finding. Additionally, we also provide evidence that 774T>C polymorphism increasing EGFR expression was not regulated by hsa-miR-214 binding. These findings suggested that EGFR 3'UTR 774T>C polymorphism may contribute to susceptibility to bladder cancer.
authors.affiliation: Department of Molecular & Genetic Toxicology, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 140 Hanzhong Road,  Nanjing 210029, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Chu
authors.forename: Meilin
authors.initials: M
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Jin
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lv
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wu
authors.forename: Na
authors.initials: N
authors.lastname: Tong
authors.forename: Lan
authors.initials: L
authors.lastname: Ma
authors.forename: Danni
authors.initials: D
authors.lastname: Shi
authors.forename: Dongyan
authors.initials: D
authors.lastname: Zhong
authors.forename: Guangbo
authors.initials: G
authors.lastname: Fu
authors.forename: Lin
authors.initials: L
authors.lastname: Yuan
authors.forename: Chao
authors.initials: C
authors.lastname: Qin
authors.forename: Changjun
authors.initials: C
authors.lastname: Yin
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions; D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C509207:MIRN124 microRNA, human; D035683:MicroRNAs; C512478:EGFR protein, human; D066246:ErbB Receptors