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Evaluation of GWAS-Identified Genetic Variants for Gastric Cancer Survival

BACKGROUNDS: Genome-wide association studies (GWASs) have identified several gastric cancer (GC) susceptibility loci in Asians, but their effects on disease outcome are still unknown. This study aimed to investigate whether these GWAS-identified genetic variants could serve as robust prognostic biom...

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Autores principales: Gu, Dongying, Zheng, Rui, Xin, Junyi, Li, Shuwei, Chu, Haiyan, Gong, Weida, Qiang, Fulin, Zhang, Zhengdong, Wang, Meilin, Du, Mulong, Chen, Jinfei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6085567/
https://www.ncbi.nlm.nih.gov/pubmed/29983348
http://dx.doi.org/10.1016/j.ebiom.2018.06.028
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author Gu, Dongying
Zheng, Rui
Xin, Junyi
Li, Shuwei
Chu, Haiyan
Gong, Weida
Qiang, Fulin
Zhang, Zhengdong
Wang, Meilin
Du, Mulong
Chen, Jinfei
author_facet Gu, Dongying
Zheng, Rui
Xin, Junyi
Li, Shuwei
Chu, Haiyan
Gong, Weida
Qiang, Fulin
Zhang, Zhengdong
Wang, Meilin
Du, Mulong
Chen, Jinfei
author_sort Gu, Dongying
collection PubMed
description BACKGROUNDS: Genome-wide association studies (GWASs) have identified several gastric cancer (GC) susceptibility loci in Asians, but their effects on disease outcome are still unknown. This study aimed to investigate whether these GWAS-identified genetic variants could serve as robust prognostic biomarkers for GC. METHODS: A multistage clinical cohort, including a total of 2432 GC patients in the Chinese population, was used to identify the association between GWAS-identified risk variants and overall survival of GC. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed by Cox regression analysis, and the log-rank P was calculated by the log-rank test with the Kaplan-Meier method. RESULTS: We found that rs2274223 A>G in PLCE1 was associated with increased GC survival in both training set (P = .011), which was independently replicated in validation set 1 (P = .045), but not in validation set 2. The area under the curve (AUC) from receiver-operator characteristic (ROC) curve showed this clinical relevance with onset age-dependence, especially in the subgroup of early-onset cases. Moreover, a significant improvement in overall survival prediction was identified when the rs2274223 genetic effect was included in the estimation; this result was also supported by the prognostic nomogram. In addition, patients with lower expression of PLCE1 showed benefits via longer survival, potentially due to the functional effect of rs2274223. INTERPRETATION: This preliminary study suggests that a GWAS-identified genetic variant in PLCE1 may serve as a potential biomarker for GC survival. Additional replication with larger samples size is warranted to further investigation.
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spelling pubmed-60855672018-08-13 Evaluation of GWAS-Identified Genetic Variants for Gastric Cancer Survival Gu, Dongying Zheng, Rui Xin, Junyi Li, Shuwei Chu, Haiyan Gong, Weida Qiang, Fulin Zhang, Zhengdong Wang, Meilin Du, Mulong Chen, Jinfei EBioMedicine Research Paper BACKGROUNDS: Genome-wide association studies (GWASs) have identified several gastric cancer (GC) susceptibility loci in Asians, but their effects on disease outcome are still unknown. This study aimed to investigate whether these GWAS-identified genetic variants could serve as robust prognostic biomarkers for GC. METHODS: A multistage clinical cohort, including a total of 2432 GC patients in the Chinese population, was used to identify the association between GWAS-identified risk variants and overall survival of GC. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed by Cox regression analysis, and the log-rank P was calculated by the log-rank test with the Kaplan-Meier method. RESULTS: We found that rs2274223 A>G in PLCE1 was associated with increased GC survival in both training set (P = .011), which was independently replicated in validation set 1 (P = .045), but not in validation set 2. The area under the curve (AUC) from receiver-operator characteristic (ROC) curve showed this clinical relevance with onset age-dependence, especially in the subgroup of early-onset cases. Moreover, a significant improvement in overall survival prediction was identified when the rs2274223 genetic effect was included in the estimation; this result was also supported by the prognostic nomogram. In addition, patients with lower expression of PLCE1 showed benefits via longer survival, potentially due to the functional effect of rs2274223. INTERPRETATION: This preliminary study suggests that a GWAS-identified genetic variant in PLCE1 may serve as a potential biomarker for GC survival. Additional replication with larger samples size is warranted to further investigation. Elsevier 2018-07-06 /pmc/articles/PMC6085567/ /pubmed/29983348 http://dx.doi.org/10.1016/j.ebiom.2018.06.028 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Gu, Dongying
Zheng, Rui
Xin, Junyi
Li, Shuwei
Chu, Haiyan
Gong, Weida
Qiang, Fulin
Zhang, Zhengdong
Wang, Meilin
Du, Mulong
Chen, Jinfei
Evaluation of GWAS-Identified Genetic Variants for Gastric Cancer Survival
title Evaluation of GWAS-Identified Genetic Variants for Gastric Cancer Survival
title_full Evaluation of GWAS-Identified Genetic Variants for Gastric Cancer Survival
title_fullStr Evaluation of GWAS-Identified Genetic Variants for Gastric Cancer Survival
title_full_unstemmed Evaluation of GWAS-Identified Genetic Variants for Gastric Cancer Survival
title_short Evaluation of GWAS-Identified Genetic Variants for Gastric Cancer Survival
title_sort evaluation of gwas-identified genetic variants for gastric cancer survival
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6085567/
https://www.ncbi.nlm.nih.gov/pubmed/29983348
http://dx.doi.org/10.1016/j.ebiom.2018.06.028
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