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PLoS One. 2014 Jun 18;9(6):e97923. doi: 10.1371/journal.pone.0097923. eCollection 2014.

Genetic variations affecting serum carcinoembryonic antigen levels and status of regional lymph nodes in patients with sporadic colorectal cancer from Southern China.

Author information

1
Department of Hepatobiliary Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
2
Department of Anal and colorectal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
3
Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
4
Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
5
Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
6
Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
7
Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, People's Republic of China; Institute of Urology and Nephrology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
8
Medical Examination Center, Fangchenggang First People's Hospital, Fangchenggang, Guangxi, People's Republic of China.
9
Medical Examination Center, Guigang First People's Hospital, Guigang, Guangxi, People's Republic of China.
10
Medical Examination Center, Yulin First People's Hospital, Yulin, Guangxi, People's Republic of China.
11
Department of Hematology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
12
Molecular Genetics Epidemiology Sec., Frederick Nat. Lab for Cancer Research, National Cancer Institute, NIH, Frederick, Maryland, United States of America.
13
Laboratory of Genomic Diversity, National Cancer Institute, NIH, Frederick, Maryland, United States of America; Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg, Russia; Oceanographic Center, Nova Southeastern University, Ft. Lauderdale, Florida, United States of America.
14
Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, People's Republic of China; Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America.
15
Department of Hepatobiliary Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China; Laboratory of Genomic Diversity, National Cancer Institute, NIH, Frederick, Maryland, United States of America.

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.

PMID:
24941225
PMCID:
PMC4062418
DOI:
10.1371/journal.pone.0097923
[Indexed for MEDLINE]
Free PMC Article

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