Document Type

Article

Publication Date

6-18-2014

Publication Title

PLoS One

Keywords

Colorectal cancer, Genome-wide associations, Genotyping, Human genetics, Lymph nodes, Metastasis, Smoking habits, Varient genotypes

ISSN

1932-6203

Volume

9

Issue/No.

6 e97923

First Page

1

Last Page

16

Abstract

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.

Comments

©2014 Liang et al. 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 credited.

Additional Comments

General Program of National Natural Science Foundation of China grant #s: 30945204, 81072321, 81272853, 81360378, 81360099, 81370857, 30760243, 30460143, 30560133; China Ministry of Education grant #: NCET2009; Key Program and University Talents Highland INnovation Team of Guangxi grant #s: 2012012D003, GJR201147-09; Chairman Science and Technology Fund and Tackle Program of Guangxi grant #s: 1116-03, GKG1298003-07-01; Guangxi Natural Science Foundation grant #s: 2011 GXNSFB018100, 2012GXNSFAA053152, 2013GXNSFFA 019002; Guangxi Nature Sciences grant #: GuiKeGong 1104003A-7; Guangxi Provincial Department of Finance and Education grant #: 2009GJCJ150; Guangxi Health Ministry Medicine Grant # Z201018; Russian Ministry of Science grant #: 11.G34.31.0068

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015

DOI

10.1371/journal.pone.0097923

Peer Reviewed

Find in your library

Share

COinS