Combination of polymorphisms within the HDAC1 and HDAC3 gene predict tumor recurrence in hepatocellular carcinoma patients that have undergone transplant therapy.
BACKGROUND
Histone deacetylases (HDACs) have been reported to be poor prognostic indicators in patients with cancer. However, no data are available for the role of single nucleotide polymorphism (SNP) of class I HDAC in hepato-cellular carcinoma (HCC). Therefore, we investigated the association of class I HDAC isoforms genomic polymorphisms with risk of HCC and tumor recurrence following liver transplantation (LT).


METHODS
One hundred and ninety-six Chinese subjects consisting of 97 HCC patients and 99 controls were enrolled in this study. Nine polymorphisms of the HDAC1, HDAC2, and HDAC3 gene (rs2530223, rs1741981, rs2547547, rs13204445, rs6568819, rs10499080, rs11741808, rs2475631, rs11391) were examined using Applied Biosystems SNaP-Shot and TaqMan technology.


RESULTS
We found no significant difference in genotype frequencies between the HCC cases and controls. In terms of tumor recurrence following LT, patients carrying the T allele of HDAC1 SNP rs1741981 showed a favorable outcome for recurrence free survival when compared with patients homozygous for CC. In addition, the same significant trend was observed in HDAC3 SNP rs2547547. Kaplan-Meier analysis showed that the combination of the T variant allele (CT+TT) of HDAC1 SNP rs1741981 and the homozygous TT variant allele of HDAC3 SNP rs2547547 was the most favorable prognostic factor. The risk for postoperative tumor recurrence was about 2.2-fold lower for patients with this genotype combination compared with carriers of the HDAC1 SNP rs1741981 CC and HDAC3 SNP rs2547547 CT genotype combination (hazard ratio: 2.235, p=0.003).


CONCLUSIONS
Our data suggest that combined analysis of HDAC1 SNP rs1741981 and HDAC3 SNP rs2547547 may be a potential genetic marker for HCC recurrence in LT patients.
Yang
Zhe
Z
Key Lab of Combined Multi-organ Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China.
Zhou
Lin
L
Wu
Li-Ming
LM
Xie
Hai-Yang
HY
Zhang
Feng
F
Zheng
Shu-Sen
SS
D044466:Asian People; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D016022:Case-Control Studies; D005838:Genotype; D056284:Histone Deacetylase 1 / Q000235:genetics*; D006655:Histone Deacetylases / Q000235:genetics*; D006801:Humans; D016031:Liver Transplantation; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011379:Prognosis; D012008:Recurrence; D000099186:Histone Deacetylase 3
D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D000099186:Histone Deacetylase 3; C110550:HDAC1 protein, human