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Cancer Med. 2017 Jul;6(7):1512-1522. doi: 10.1002/cam4.1067. Epub 2017 Jun 22.

Genetic variants of cell cycle pathway genes predict disease-free survival of hepatocellular carcinoma.

Author information

1
Department of Epidemiology, School of Public Health, Guangxi Medical University, 22 Shuangyong Road, Nanning, Guangxi, 530021, China.
2
Affiliated Tumor Hospital of Guangxi Medical University, 71 Hedi Road, Nanning, Guangxi, 530021, China.
3
Shenzhen Longhua Center for Chronic Diseases Prevention and Control, 118 Guanlan Road, Shenzhen, Guangdong, 518110, China.
4
GuangXi Center for Disease Prevention and Control, 18 Jinzhou Road, Nanning, Guangxi, 530021, China.
5
Medical Scientific Research Centre, Guangxi Medical University, 22 Shuangyong Road, Nanning, Guangxi, 530021, China.

Abstract

Disruption of the cell cycle pathway has previously been related to development of human cancers. However, associations between genetic variants of cell cycle pathway genes and prognosis of hepatocellular carcinoma (HCC) remain largely unknown. In this study, we evaluated the associations between 24 potential functional single nucleotide polymorphisms (SNPs) of 16 main cell cycle pathway genes and disease-free survival (DFS) of 271 HCC patients who had undergone radical surgery resection. We identified two SNPs, i.e., SMAD3 rs11556090 A>G and RBL2 rs3929G>C, that were independently predictive of DFS in an additive genetic model with false-positive report probability (FPRP) <0.2. The SMAD3 rs11556090G allele was associated with a poorer DFS, compared with the A allele [hazard ratio (HR) = 1.46, 95% confidential interval (95% CI) = 1.13-1.89, P = 0.004]; while the RBL2 rs3929 C allele was associated with a superior DFS, compared with the G allele (HR = 0.74, 95% CI = 0.57-0.96, P = 0.023). Additionally, patients with an increasing number of unfavorable genotypes (NUGs) of these loci had a significant shorter DFS (Ptrend  = 0.0001). Further analysis using receiver operating characteristic (ROC) curves showed that the model including the NUGs and known prognostic clinical variables demonstrated a significant improvement in predicting the 1-year DFS (P = 0.011). Moreover, the RBL2 rs3929 C allele was significantly associated with increased mRNA expression levels of RBL2 in liver tissue (P = 1.8 × 10-7 ) and the whole blood (P = 3.9 × 10-14 ). Our data demonstrated an independent or a joint effect of SMAD3 rs11556090 and RBL2 rs3929 in the cell cycle pathway on DFS of HCC, which need to be validated by large cohort and biological studies.

KEYWORDS:

Cell cycle pathway; hepatocellular carcinoma; single-nucleotide polymorphism; survival

PMID:
28639733
PMCID:
PMC5504311
DOI:
10.1002/cam4.1067
[Indexed for MEDLINE]
Free PMC Article

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