Functional Genetic Variant of WW Domain-containing Oxidoreductase (WWOX) Gene is Associated with Hepatocellular Carcinoma Risk

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2017 Apr 21

PMID 28426730

Citations 12

Authors

Hsiang-Lin Lee

Hsin-Lin Cheng

Yu-Fan Liu

Ming-Chih Chou

Shun-Fa Yang

Ying-Erh Chou

Affiliations

Soon will be listed here.

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Human WW domain-containing oxidoreductase (WWOX) gene has been identified as a tumor suppressor gene in multiple cancers. We hypothesize that genetic variations in WWOX are associated with HCC risk.

Methodology/principal Findings: Five single-nucleotide polymorphisms (SNPs) of the WWOX gene were evaluated from 708 normal controls and 354 patients with HCC. We identified a significant association between a WWOX single nucleotide polymorphism (SNP), rs73569323, and decreased risk of HCC. After adjustment for potential confounders, patients with at least one T allele at rs11545028 of WWOX may have a significantly smaller tumor size, reduced levels of α-fetoprotein and alanine aminotransferase (ALT). Moreover, the A allele at SNP rs12918952 in WWOX conferred higher risk of vascular invasion. Additional in silico analysis also suggests that WWOX rs12918952 polymorphism tends to affect WWOX expression, which in turn contributes to tumor vascular invasion.

Conclusions: In conclusion, genetic variations in WWOX may be a significant predictor of early HCC occurrence and a reliable biomarker for disease progression.

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