title: A single nucleotide polymorphism in the 3'-UTR of STAT3 regulates its expression and reduces risk of pancreatic cancer in a Chinese population.
abstract: Pancreatic cancer (PC) is one of the deadliest solid malignancies carrying a gloomy 5-year survival rate less than 5%. The signal transducer and activator of transcription 3 (STAT3) is a common transcriptional regulator, whose aberrant expression has been widely found in human cancers, including PC. Our current study aimed to illustrate the roles of common variants, in the three prime untranslated region (3'UTR) of STAT3, in modifying the risk of PC through two-stage case-control studies integrating biological experiments. We first explored the associations between two common variants (rs1053004 and rs1053005) and PC risk in 774 PC cases and 777 controls. Only rs1053004 T > C showed a significant association with a reduced risk of PC with an odds ratio (OR) and 95% confidence interval (CI) of 0.85 (0.74-0.98). Then we attempted to validate the association in another 940 cases and 1398 controls, and the significant association persisted with OR (95%CI) of 0.86 (0.76-0.97). Dual luciferase reporter gene assays indicated that C allele conferred a higher expression of STAT3 in three PC cell lines including Panc-1 (P = 3.0 × 10-3), BxPC-3 (P = 6.7 × 10-5) and SW1990 (P = 4.0 × 10-3). In conclusion, the current study provided evidence that rs1053004 T > C in 3'UTR of STAT3 may decrease the risk of PC through up-regulating the gene expression.
authors: State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Beibei
authors: B
authors: Zhu
authors: State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Ying
authors: Y
authors: Zhu
authors: State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Jiao
authors: J
authors: Lou
authors: State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Juntao
authors: J
authors: Ke
authors: State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Yi
authors: Y
authors: Zhang
authors: State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Jiaoyuan
authors: J
authors: Li
authors: State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Yajie
authors: Y
authors: Gong
authors: State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Yang
authors: Y
authors: Yang
authors: State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Jianbo
authors: J
authors: Tian
authors: State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Xiating
authors: X
authors: Peng
authors: State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Danyi
authors: D
authors: Zou
authors: State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Rong
authors: R
authors: Zhong
authors: State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Jing
authors: J
authors: Gong
authors: State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Jiang
authors: J
authors: Chang
authors: State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, China.
authors: Lu
authors: L
authors: Li
authors: State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Xiaoping
authors: X
authors: Miao
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010190:Pancreatic Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: STAT3; case-control study; genetic variants; pancreatic cancer; susceptibility