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Genetic Variations Affecting Serum Carcinoembryonic Antigen Levels and Status of Regional Lymph Nodes in Patients with Sporadic Colorectal Cancer from Southern China

BACKGROUND: Serum carcinoembryonic antigen (sCEA) level might be an indicator of disease. Indeed, an elevated sCEA level is a prognostic factor in colorectal cancer (CRC) patients. However, the genetic determinants of sCEA level in healthy and CRC population remains unclear. Thus we investigated the...

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Autores principales: Liang, Yu, Tang, Weizhong, Huang, Tiqiang, Gao, Yong, Tan, Aihua, Yang, Xiaobo, Zhang, Haiying, Hu, Yanling, Qin, Xue, Li, Shan, Zhang, Shijun, Mo, Linjian, Liang, Zhenjia, Shi, Deyi, Huang, Zhang, Guan, Yingyong, Zhou, Jicheng, Winkler, Cheryl, O'Brien, Stephen J., Xu, Jianfeng, Mo, Zengnan, Peng, Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4062418/
https://www.ncbi.nlm.nih.gov/pubmed/24941225
http://dx.doi.org/10.1371/journal.pone.0097923
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author Liang, Yu
Tang, Weizhong
Huang, Tiqiang
Gao, Yong
Tan, Aihua
Yang, Xiaobo
Zhang, Haiying
Hu, Yanling
Qin, Xue
Li, Shan
Zhang, Shijun
Mo, Linjian
Liang, Zhenjia
Shi, Deyi
Huang, Zhang
Guan, Yingyong
Zhou, Jicheng
Winkler, Cheryl
O'Brien, Stephen J.
Xu, Jianfeng
Mo, Zengnan
Peng, Tao
author_facet Liang, Yu
Tang, Weizhong
Huang, Tiqiang
Gao, Yong
Tan, Aihua
Yang, Xiaobo
Zhang, Haiying
Hu, Yanling
Qin, Xue
Li, Shan
Zhang, Shijun
Mo, Linjian
Liang, Zhenjia
Shi, Deyi
Huang, Zhang
Guan, Yingyong
Zhou, Jicheng
Winkler, Cheryl
O'Brien, Stephen J.
Xu, Jianfeng
Mo, Zengnan
Peng, Tao
author_sort Liang, Yu
collection PubMed
description BACKGROUND: Serum carcinoembryonic antigen (sCEA) level might be an indicator of disease. Indeed, an elevated sCEA level is a prognostic factor in colorectal cancer (CRC) patients. However, the genetic determinants of sCEA level in healthy and CRC population remains unclear. Thus we investigated the genetic markers associated with elevated serum sCEA level in these two populations and its clinical implications. METHODS AND FINDINGS: Genome-wide association study (GWAS) was conducted in a cohort study with 4,346 healthy male adults using the Illumina Omni 1 M chip. Candidate SNPs associated with elevated sCEA levels were validated in 194 CRC patients on ABI Taqman platform. Eight candidate SNPs were validated in CRC patients. The rs1047781 (chr19- FUT2) (A/T) was associated with elevated sCEA levels, and rs8176746 (chr9- ABO) was associated with the regional lymph metastasis in the CRC patients. The preoperative sCEA level was a risk factor for tumor recurrence in 5 years after operation (OR = 1.427, 95% CI: 1.005∼1.843, P = 0.006). It was also one of the risk factors for regional lymph node metastasis (OR = 2.266, 95% CI: 1.196∼4.293, P = 0.012). The sCEA level in rs1047781-T carriers was higher than that in the A carriers in CRC patients without lymph node metastasis (P = 0.006). The regional lymph node metastasis in patients with homozygote AA of rs8176746 was more common than that in the heterozygote AG carriers (P = 0.022). In addition, rs1047781-AT and TT CRC patients exhibited a worse disease-free survival than AA genotype carriers (P = 0.023). CONCLUSIONS: We found candidate SNPs associated with elevated sCEA levels in both healthy males and CRC population. Rs1047781 (chr19- FUT2) may be the susceptible locus for recurrence of CRC in a population from Southern China.
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spelling pubmed-40624182014-06-24 Genetic Variations Affecting Serum Carcinoembryonic Antigen Levels and Status of Regional Lymph Nodes in Patients with Sporadic Colorectal Cancer from Southern China Liang, Yu Tang, Weizhong Huang, Tiqiang Gao, Yong Tan, Aihua Yang, Xiaobo Zhang, Haiying Hu, Yanling Qin, Xue Li, Shan Zhang, Shijun Mo, Linjian Liang, Zhenjia Shi, Deyi Huang, Zhang Guan, Yingyong Zhou, Jicheng Winkler, Cheryl O'Brien, Stephen J. Xu, Jianfeng Mo, Zengnan Peng, Tao PLoS One Research Article BACKGROUND: Serum carcinoembryonic antigen (sCEA) level might be an indicator of disease. Indeed, an elevated sCEA level is a prognostic factor in colorectal cancer (CRC) patients. However, the genetic determinants of sCEA level in healthy and CRC population remains unclear. Thus we investigated the genetic markers associated with elevated serum sCEA level in these two populations and its clinical implications. METHODS AND FINDINGS: Genome-wide association study (GWAS) was conducted in a cohort study with 4,346 healthy male adults using the Illumina Omni 1 M chip. Candidate SNPs associated with elevated sCEA levels were validated in 194 CRC patients on ABI Taqman platform. Eight candidate SNPs were validated in CRC patients. The rs1047781 (chr19- FUT2) (A/T) was associated with elevated sCEA levels, and rs8176746 (chr9- ABO) was associated with the regional lymph metastasis in the CRC patients. The preoperative sCEA level was a risk factor for tumor recurrence in 5 years after operation (OR = 1.427, 95% CI: 1.005∼1.843, P = 0.006). It was also one of the risk factors for regional lymph node metastasis (OR = 2.266, 95% CI: 1.196∼4.293, P = 0.012). The sCEA level in rs1047781-T carriers was higher than that in the A carriers in CRC patients without lymph node metastasis (P = 0.006). The regional lymph node metastasis in patients with homozygote AA of rs8176746 was more common than that in the heterozygote AG carriers (P = 0.022). In addition, rs1047781-AT and TT CRC patients exhibited a worse disease-free survival than AA genotype carriers (P = 0.023). CONCLUSIONS: We found candidate SNPs associated with elevated sCEA levels in both healthy males and CRC population. Rs1047781 (chr19- FUT2) may be the susceptible locus for recurrence of CRC in a population from Southern China. Public Library of Science 2014-06-18 /pmc/articles/PMC4062418/ /pubmed/24941225 http://dx.doi.org/10.1371/journal.pone.0097923 Text en © 2014 Liang 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Liang, Yu
Tang, Weizhong
Huang, Tiqiang
Gao, Yong
Tan, Aihua
Yang, Xiaobo
Zhang, Haiying
Hu, Yanling
Qin, Xue
Li, Shan
Zhang, Shijun
Mo, Linjian
Liang, Zhenjia
Shi, Deyi
Huang, Zhang
Guan, Yingyong
Zhou, Jicheng
Winkler, Cheryl
O'Brien, Stephen J.
Xu, Jianfeng
Mo, Zengnan
Peng, Tao
Genetic Variations Affecting Serum Carcinoembryonic Antigen Levels and Status of Regional Lymph Nodes in Patients with Sporadic Colorectal Cancer from Southern China
title Genetic Variations Affecting Serum Carcinoembryonic Antigen Levels and Status of Regional Lymph Nodes in Patients with Sporadic Colorectal Cancer from Southern China
title_full Genetic Variations Affecting Serum Carcinoembryonic Antigen Levels and Status of Regional Lymph Nodes in Patients with Sporadic Colorectal Cancer from Southern China
title_fullStr Genetic Variations Affecting Serum Carcinoembryonic Antigen Levels and Status of Regional Lymph Nodes in Patients with Sporadic Colorectal Cancer from Southern China
title_full_unstemmed Genetic Variations Affecting Serum Carcinoembryonic Antigen Levels and Status of Regional Lymph Nodes in Patients with Sporadic Colorectal Cancer from Southern China
title_short Genetic Variations Affecting Serum Carcinoembryonic Antigen Levels and Status of Regional Lymph Nodes in Patients with Sporadic Colorectal Cancer from Southern China
title_sort genetic variations affecting serum carcinoembryonic antigen levels and status of regional lymph nodes in patients with sporadic colorectal cancer from southern china
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4062418/
https://www.ncbi.nlm.nih.gov/pubmed/24941225
http://dx.doi.org/10.1371/journal.pone.0097923
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