title: Functional short tandem repeat polymorphism of PTPN11 and susceptibility to hepatocellular carcinoma in Chinese populations.
abstract: BACKGROUND
  PTPN11, which encodes tyrosine phosphatase Shp2, is a critical gene mediating cellular responses to hormones and cytokines. Loss of Shp2 promotes hepatocellular carcinoma (HCC), suggesting that PTPN11 functions as a tumor suppressor in HCC tumorgenesis. The aim of this study was to evaluate the effects of the short tandem repeat (STR) polymorphism (rs199618935) within 3'UTR of PTPN11 on HCC susceptibility in Chinese populations.
  
  
  RESULTS
  We analyzed the associations in 400 patients from Jiangsu province of China, validating the findings in an additional 305 patients from Shanghai of China. Unconditional logistic regression was used to analyze the association between rs199618935 and HCC risk. Additional biochemical investigations and in-silico studies were used to evaluate the possible functional significance of this polymorphism. Logistic regression analysis showed that compared with individuals carrying shorter alleles (11 and 12 repeats), those subjects who carry longer alleles (13 and 14 repeats) had a significantly decreased risk of HCC [adjusted odds ratio (OR) = 0.63, 95% confidence interval (CI)  = 0.53-0.76, P = 2.00 × 10(-7)], with the risk decreased even further in those carrying allele 15 and 16 (adjusted OR = 0.46, 95% CI = 0.34-0.62, P = 1.00 × 10(-7)). Biochemical investigations showed that longer alleles of rs199618935 conferred higher PTPN11 expression in vivo and in vitro. The altered luciferase activities in reporter gene system suggested that STR regulation of PTPN11 expression could be a transcriptional event. Finally, in-silico prediction revealed that different alleles of rs199618935 could alter the local structure of PTPN11 mRNA.
  
  
  CONCLUSIONS
  Taken together, our findings suggested that the STR polymorphism within PTPN11 contributes to hepatocarcinogenesis, possibly by affecting PTPN11 expression through a structure-dependent mechanism. The replication of our studies and further functional studies are needed to validate our findings.
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou, Jiangsu, P.R. China.
authors.forename: Xiankun
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou, Jiangsu, P.R. China.
authors.forename: Shuxiang
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou, Jiangsu, P.R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou, Jiangsu, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou, Jiangsu, P.R. China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou, Jiangsu, P.R. China.
authors.forename: Chaoqun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou, Jiangsu, P.R. China.
authors.forename: Ruiyang
authors.initials: R
authors.lastname: Tao
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou, Jiangsu, P.R. China.
authors.forename: Siping
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou, Jiangsu, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Medical Molecular Virology, MOE & MOH, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Jiejie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Epidemiology, Medical College of Soochow University, Suzhou, Jiangsu, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou, Jiangsu, P.R. China.
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Gao
mesh_terms: D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D017931:DNA Primers; D020022:Genetic Predisposition to Disease; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D018895:Microsatellite Repeats; D011110:Polymorphism, Genetic; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11