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Molecular Cancer
Published in: Molecular Cancer 1/2015

Open Access 01-12-2015 | Research

Genetic variations in genes of metabolic enzymes predict postoperational prognosis of patients with colorectal cancer

Authors: Guanglong Dong, Xianli He, Yibing Chen, Haiyan Cao, Jiaojiao Wang, Xiaonan Liu, Shukui Wang, Shaogui Wan, Jinliang Xing

Published in: Molecular Cancer | Issue 1/2015

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Abstract

Background

Genetic alterations in tricarboxylic acid (TCA) cycle metabolic enzymes were recently linked to various cancers. However, the associations of single nucleotide polymorphisms (SNPs) in genes of these enzymes have not been well studied.

Methods

We genotyped 16 SNPs from 7 genes encoding TCA cycle metabolic enzymes in 697 colorectal carcinoma (CRC) patients receiving surgical resection and analyzed their associations with clinical outcomes by multivariate Cox proportional hazard model. Then, the significant results were validated in another cohort of 256 CRC patients.

Results

We identified 4 SNPs in 2 genes had significant associations with CRC death risk and 5 SNPs in 3 genes had significant associations with CRC recurrence risk. Similar significant results were confirmed for rs4131826 in SDHC gene, rs544184 in SDHD gene and rs12071124 in FH gene in a validation cohort. Further analysis indicated that unfavorable genotypes exhibited a significant cumulative effect on overall and recurrence-free survival in a dose-dependent manner. Moreover, survival tree analysis indicated that SNP rs4131826 in SDHC gene and SNP rs12071124 in FH gene were the primary factors contributing to the different overall survival time and recurrence-free survival time of CRC patients, respectively. Immunohistochemical analysis further validated the effect of rs4131826 and rs544184 on expression of SDHC and SDHD in tissue samples.

Conclusions

Our study suggests that SNPs in TCA cycle metabolic enzymes might be significantly associated with clinical outcomes in Chinese population diagnosed with CRC. Further functional and validated studies are warranted to expend our results to clinical utility.
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Metadata
Title
Genetic variations in genes of metabolic enzymes predict postoperational prognosis of patients with colorectal cancer
Authors
Guanglong Dong
Xianli He
Yibing Chen
Haiyan Cao
Jiaojiao Wang
Xiaonan Liu
Shukui Wang
Shaogui Wan
Jinliang Xing
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2015
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-015-0442-x

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