Association of hOGG1 Ser326Cys, ITGA2 C807T, TNF-A -308G>A and XPD Lys751Gln polymorphisms with the survival of Malaysian NPC patients.

BACKGROUND:Nasopharyngeal carcinoma is a rare form of cancer across the world except in certain areas such as Southern China, Hong Kong and Malaysia. NPC is considered a relatively radiosensitive tumor and patients diagnosed at early stages tend to survive longer compared to those with advanced dise...

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Main Authors: Eng-Zhuan Ban, Munn-Sann Lye, Pei Pei Chong, Yoke-Yeow Yap, Siew Ying Crystale Lim, Hejar Abdul Rahman
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC6005472?pdf=render
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spelling doaj-05ab7561da7f483f9f92004e60b69f762020-11-24T22:12:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01136e019833210.1371/journal.pone.0198332Association of hOGG1 Ser326Cys, ITGA2 C807T, TNF-A -308G>A and XPD Lys751Gln polymorphisms with the survival of Malaysian NPC patients.Eng-Zhuan BanMunn-Sann LyePei Pei ChongYoke-Yeow YapSiew Ying Crystale LimHejar Abdul RahmanBACKGROUND:Nasopharyngeal carcinoma is a rare form of cancer across the world except in certain areas such as Southern China, Hong Kong and Malaysia. NPC is considered a relatively radiosensitive tumor and patients diagnosed at early stages tend to survive longer compared to those with advanced disease. Given that early symptoms of NPC are non-specific and that the nasopharynx is relatively inaccessible, less invasive screening methods such as biomarker screening might be the key to improve NPC survival and management. A number of genes with their respective polymorphisms have been shown in past studies to be associated with survival of various cancers. hOGG1 and XPD genes encode for a DNA glycosylase and a DNA helicase respectively; both are proteins that are involved in DNA repair. ITGA2 is the alpha subunit of the transmembrane receptor integrin and is mainly responsible for cell-cell and cell-extracellular matrix interaction. TNF-α is a cytokine that is released by immune cells during inflammation. METHODS:Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) was used to genotype all the aforementioned gene polymorphisms. Kaplan-Meier survival function, log-rank test and Cox regression were used to investigate the effect of gene polymorphisms on the all-cause survival of NPC. RESULTS:NPC cases carrying T/T genotype of ITGA2 C807T have poorer all-cause survival compared to those with C/C genotypes, with an adjusted HR of 2.06 (95% CI = 1.14-3.72) in individual model. The 5-year survival rate of C/C carriers was 55% compared to those with C/T and T/T where the survival rates were 50% and 43%, respectively. CONCLUSION:The finding from the present study showed that ITGA2 C807T polymorphism could be potentially useful as a prognostic biomarker for NPC. However, the prognostic value of ITGA2 C807T polymorphism has to be validated by well-designed further studies with larger patient numbers.http://europepmc.org/articles/PMC6005472?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Eng-Zhuan Ban
Munn-Sann Lye
Pei Pei Chong
Yoke-Yeow Yap
Siew Ying Crystale Lim
Hejar Abdul Rahman
spellingShingle Eng-Zhuan Ban
Munn-Sann Lye
Pei Pei Chong
Yoke-Yeow Yap
Siew Ying Crystale Lim
Hejar Abdul Rahman
Association of hOGG1 Ser326Cys, ITGA2 C807T, TNF-A -308G>A and XPD Lys751Gln polymorphisms with the survival of Malaysian NPC patients.
PLoS ONE
author_facet Eng-Zhuan Ban
Munn-Sann Lye
Pei Pei Chong
Yoke-Yeow Yap
Siew Ying Crystale Lim
Hejar Abdul Rahman
author_sort Eng-Zhuan Ban
title Association of hOGG1 Ser326Cys, ITGA2 C807T, TNF-A -308G>A and XPD Lys751Gln polymorphisms with the survival of Malaysian NPC patients.
title_short Association of hOGG1 Ser326Cys, ITGA2 C807T, TNF-A -308G>A and XPD Lys751Gln polymorphisms with the survival of Malaysian NPC patients.
title_full Association of hOGG1 Ser326Cys, ITGA2 C807T, TNF-A -308G>A and XPD Lys751Gln polymorphisms with the survival of Malaysian NPC patients.
title_fullStr Association of hOGG1 Ser326Cys, ITGA2 C807T, TNF-A -308G>A and XPD Lys751Gln polymorphisms with the survival of Malaysian NPC patients.
title_full_unstemmed Association of hOGG1 Ser326Cys, ITGA2 C807T, TNF-A -308G>A and XPD Lys751Gln polymorphisms with the survival of Malaysian NPC patients.
title_sort association of hogg1 ser326cys, itga2 c807t, tnf-a -308g>a and xpd lys751gln polymorphisms with the survival of malaysian npc patients.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2018-01-01
description BACKGROUND:Nasopharyngeal carcinoma is a rare form of cancer across the world except in certain areas such as Southern China, Hong Kong and Malaysia. NPC is considered a relatively radiosensitive tumor and patients diagnosed at early stages tend to survive longer compared to those with advanced disease. Given that early symptoms of NPC are non-specific and that the nasopharynx is relatively inaccessible, less invasive screening methods such as biomarker screening might be the key to improve NPC survival and management. A number of genes with their respective polymorphisms have been shown in past studies to be associated with survival of various cancers. hOGG1 and XPD genes encode for a DNA glycosylase and a DNA helicase respectively; both are proteins that are involved in DNA repair. ITGA2 is the alpha subunit of the transmembrane receptor integrin and is mainly responsible for cell-cell and cell-extracellular matrix interaction. TNF-α is a cytokine that is released by immune cells during inflammation. METHODS:Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) was used to genotype all the aforementioned gene polymorphisms. Kaplan-Meier survival function, log-rank test and Cox regression were used to investigate the effect of gene polymorphisms on the all-cause survival of NPC. RESULTS:NPC cases carrying T/T genotype of ITGA2 C807T have poorer all-cause survival compared to those with C/C genotypes, with an adjusted HR of 2.06 (95% CI = 1.14-3.72) in individual model. The 5-year survival rate of C/C carriers was 55% compared to those with C/T and T/T where the survival rates were 50% and 43%, respectively. CONCLUSION:The finding from the present study showed that ITGA2 C807T polymorphism could be potentially useful as a prognostic biomarker for NPC. However, the prognostic value of ITGA2 C807T polymorphism has to be validated by well-designed further studies with larger patient numbers.
url http://europepmc.org/articles/PMC6005472?pdf=render
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