title: Association between donor and recipient smoothened gene polymorphisms and the risk of hepatocellular carcinoma recurrence following orthotopic liver transplantation in a Han Chinese population.
abstract: Hepatocellular carcinoma (HCC) recurrence after orthotopic liver transplantation (OLT) is potential cause for the poor outcome. Smoothened (SMO) gene has been considered associating with HCC and HCC recurrence, but its association with HCC recurrence after OLT is not clear yet. In this study, we aim at evaluating the association between donor and recipient SMO gene polymorphisms and HCC recurrence after OLT. A total of 76 patients with HCC who had undergone OLT from July 2007 to August 2012 were included. A single nucleotide polymorphism (SNP), SMO rs3824, located at the 3'UTR region, was genotyped and analyzed in both donor and recipient. We demonstrated that recipient rs3824 polymorphism was significantly associated with HCC recurrence following OLT. In multivariate logistic regression analysis, TNM stage (p = 0.001), recipient SMO rs3824 genotype (CG vs. CC/GG p = 0.001), and histologic grade (p = 0.019) were identified as independent risk factors of HCC recurrence. Recurrence-free survival (RFS) and overall survival (OS) were significantly higher in the recipient CC/GG group than in the CG group (p = 0.003 and p = 0.011, respectively). Cox proportional hazards modeling revealed that TNM stage, recipient SMO rs3824 genotype, pre-OLT serum AFP level, and histologic grade were independent factors (p < 0.05) for patients' clinical outcomes. In conclusion, recipient SMO rs3824 polymorphism is associated with an increased risk of HCC recurrence following OLT and has a potential clinical value for the prognosis of HCC patients treated with OLT.
authors.affiliation: Department of General Surgery, Affiliated First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China.
authors.forename: Pusen
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The First People's Hospital of Yongkang City, Yongkang City, Zhejiang Province, 321300, China.
authors.forename: Weiyong
authors.initials: W
authors.lastname: Song
authors.affiliation: Department of General Surgery, Affiliated First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of General Surgery, Affiliated First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China.
authors.forename: Cunguang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Affiliated First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China.
authors.forename: Baojie
authors.initials: B
authors.lastname: Shi
authors.affiliation: Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation, The first Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, China. guowz_wps@hotmail.com.
authors.forename: Wenzhi
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of General Surgery, Affiliated First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China. zhongl_3284@hotmail.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhong
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000628:therapy / Q000821:virology; D002681:China / Q000453:epidemiology; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy / Q000821:virology; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D012307:Risk Factors; D000072086:Smoothened Receptor; D015996:Survival Rate; D014019:Tissue Donors
chemical_list: D004273:DNA, Neoplasm; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; D000072086:Smoothened Receptor
keywords: Hepatocellular carcinoma; Orthotopic liver transplantation; Prognosis; Recurrence; SMO polymorphism