C Wang1, H Xie1, D Lu1, Q Ling1, P Jin1, H Li2, R Zhuang1, X Xu1, S Zheng3. 1. Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. 2. Shenzhen Key Laboratory of Hepatobiliary Disease, Shenzhen Third People's Hospital, Shenzhen, China. 3. Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. shusenzheng@zju.edu.cn.
Abstract
BACKGROUND: Methylenetetrahyfrofolate reductase (MTHFR) is the key enzyme for one carbon and folate metabolism. Previous studies have drawn different conclusions about the relationship between the mutation of MTHFR and hepatocellular carcinoma (HCC) occurrence. MTHFR polymorphisms' influence on liver transplantation for HCC recurrence has yet not been reported. Aim of this study was to clarify the impact of MTHFR polymorphism on hepatocarcinogenesis and the prognosis of liver transplant recipient with HCC. METHODS: This study enrolled 244 HCC patients and 487 healthy individuals in Chinese Han population to analyze the influence of MTHFR polymorphism on HCC susceptibility first. Furthermore, this research choose another 100 donors' and 104 recipients' specimens to detect the association between polymorphism of MTHFR and post-transplant HCC recurrence. RESULT: rs1801131 polymorphism A to C was associated with the occurrence of HCC in Chinese Han population (p < 0.05), especially in age exceeding 50 years (p < 0.01). No association was observed with rs1801133 polymorphism and HCC occurrence. The mean tumor-free survival for recipients with donor liver graft rs1801133 C to T variants was shorter than CC type (12.63 ± 3.84 vs 22.43 ± 4.74 months, p < 0.05). Multivariate analysis revealed that Donor rs1801133 and Hangzhou criteria were two independent prognostic factors for tumor-free survival (p < 0.05). Neither donor rs1801131 polymorphism nor recipients' MTHFR polymorphisms was associated with HCC recurrence. CONCLUSION: This study demonstrated that MTHFR polymorphism was associated with HCC occurrence and post-transplant HCC recurrence. rs1801131 mutation A to C is a valuable molecular biomarker for predicting HCC occurrence in Chinese Han population. Donor MTHFR rs1801133 C to T polymorphism could present as a promising prognostic biomarkers for HCC recurrence in liver transplant recipients.
BACKGROUND:Methylenetetrahyfrofolate reductase (MTHFR) is the key enzyme for one carbon and folate metabolism. Previous studies have drawn different conclusions about the relationship between the mutation of MTHFR and hepatocellular carcinoma (HCC) occurrence. MTHFR polymorphisms' influence on liver transplantation for HCC recurrence has yet not been reported. Aim of this study was to clarify the impact of MTHFR polymorphism on hepatocarcinogenesis and the prognosis of liver transplant recipient with HCC. METHODS: This study enrolled 244 HCC patients and 487 healthy individuals in Chinese Han population to analyze the influence of MTHFR polymorphism on HCC susceptibility first. Furthermore, this research choose another 100 donors' and 104 recipients' specimens to detect the association between polymorphism of MTHFR and post-transplant HCC recurrence. RESULT: rs1801131 polymorphism A to C was associated with the occurrence of HCC in Chinese Han population (p < 0.05), especially in age exceeding 50 years (p < 0.01). No association was observed with rs1801133 polymorphism and HCC occurrence. The mean tumor-free survival for recipients with donor liver graft rs1801133 C to T variants was shorter than CC type (12.63 ± 3.84 vs 22.43 ± 4.74 months, p < 0.05). Multivariate analysis revealed that Donorrs1801133 and Hangzhou criteria were two independent prognostic factors for tumor-free survival (p < 0.05). Neither donorrs1801131 polymorphism nor recipients' MTHFR polymorphisms was associated with HCC recurrence. CONCLUSION: This study demonstrated that MTHFR polymorphism was associated with HCC occurrence and post-transplant HCC recurrence. rs1801131 mutation A to C is a valuable molecular biomarker for predicting HCC occurrence in Chinese Han population. DonorMTHFRrs1801133 C to T polymorphism could present as a promising prognostic biomarkers for HCC recurrence in liver transplant recipients.
Entities:
Keywords:
Cancer recurrence; Liver cancer; Liver transplantation; MTHFR; Single nucleotide polymorphism
Authors: Sun Young Kwak; Un Kyung Kim; Hyo Jin Cho; Hee Keun Lee; Hye Jin Kim; Nam Keun Kim; Seong Gyu Hwang Journal: Anticancer Res Date: 2008 Sep-Oct Impact factor: 2.480