MDR1 gene polymorphisms and risk of recurrence in patients with hepatocellular carcinoma after liver transplantation.
OBJECTIVE
Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains a major cause of post-LT death. However, currently there is still lacking the markers to reliably predict recurrence. This study was undertaken to evaluate the association between three polymorphisms (C1236T, G2677A/T, C3435T) of Multidrug resistance 1 (MDR1) gene and the risk of recurrence after LT.


METHODS
Genomic DNA of 99 HCC patients undergoing LT was extracted from peripheral blood lymphocytes and genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism assay. Cox proportional hazard model was used to estimate the hazard ratios associated with polymorphisms.


RESULTS
During a mean follow-up of 14.9 months, 49 patients experienced recurrence. The association between recurrence-free and 2677A carrier (carrying at least one variant A allele) was significant (P = 0.019). However, no significant association was observed in other polymorphisms. Patients with 2677A carrier conferred a 63% reduction in recurrence risk compared with 2677A non-carrier (odds ratio: 0.374; 95% confidence interval: 0.177-0.788; P = 0.010). The median recurrence-free survival for 2677A carrier group was significantly longer than that for 2677A non-carrier group (44.2 vs. 10.5 months, P = 0.015).


CONCLUSIONS
The polymorphism of MDR1 gene may be a valuable molecular marker for HCC recurrence after LT.
Wu
Liming
L
Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
Xu
Xiaobo
X
Shen
Juwei
J
Xie
Haiyang
H
Yu
Songfeng
S
Liang
Tingbo
T
Wang
Weilin
W
Shen
Yan
Y
Zhang
Min
M
Zheng
Shusen
S
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000601:surgery; D005260:Female; D019450:Genes, MDR; D005838:Genotype; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012306:Risk
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1