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Functional genetic variant of WW domain-containing oxidoreductase (WWOX) gene is associated with hepatocellular carcinoma risk
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. METH...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5398630/ https://www.ncbi.nlm.nih.gov/pubmed/28426730 http://dx.doi.org/10.1371/journal.pone.0176141 |
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author | Lee, Hsiang-Lin Cheng, Hsin-Lin Liu, Yu-Fan Chou, Ming-Chih Yang, Shun-Fa Chou, Ying-Erh |
author_facet | Lee, Hsiang-Lin Cheng, Hsin-Lin Liu, Yu-Fan Chou, Ming-Chih Yang, Shun-Fa Chou, Ying-Erh |
author_sort | Lee, Hsiang-Lin |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5398630 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-53986302017-05-04 Functional genetic variant of WW domain-containing oxidoreductase (WWOX) gene is associated with hepatocellular carcinoma risk Lee, Hsiang-Lin Cheng, Hsin-Lin Liu, Yu-Fan Chou, Ming-Chih Yang, Shun-Fa Chou, Ying-Erh PLoS One Research Article 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. Public Library of Science 2017-04-20 /pmc/articles/PMC5398630/ /pubmed/28426730 http://dx.doi.org/10.1371/journal.pone.0176141 Text en © 2017 Lee et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Lee, Hsiang-Lin Cheng, Hsin-Lin Liu, Yu-Fan Chou, Ming-Chih Yang, Shun-Fa Chou, Ying-Erh Functional genetic variant of WW domain-containing oxidoreductase (WWOX) gene is associated with hepatocellular carcinoma risk |
title | Functional genetic variant of WW domain-containing oxidoreductase (WWOX) gene is associated with hepatocellular carcinoma risk |
title_full | Functional genetic variant of WW domain-containing oxidoreductase (WWOX) gene is associated with hepatocellular carcinoma risk |
title_fullStr | Functional genetic variant of WW domain-containing oxidoreductase (WWOX) gene is associated with hepatocellular carcinoma risk |
title_full_unstemmed | Functional genetic variant of WW domain-containing oxidoreductase (WWOX) gene is associated with hepatocellular carcinoma risk |
title_short | Functional genetic variant of WW domain-containing oxidoreductase (WWOX) gene is associated with hepatocellular carcinoma risk |
title_sort | functional genetic variant of ww domain-containing oxidoreductase (wwox) gene is associated with hepatocellular carcinoma risk |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5398630/ https://www.ncbi.nlm.nih.gov/pubmed/28426730 http://dx.doi.org/10.1371/journal.pone.0176141 |
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