1. Genetic variations affecting serum carcinoembryonic antigen levels and status of regional lymph nodes in patients with sporadic colorectal cancer from Southern China.
- Author
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Liang Y, Tang W, Huang T, Gao Y, Tan A, Yang X, Zhang H, Hu Y, Qin X, Li S, Zhang S, Mo L, Liang Z, Shi D, Huang Z, Guan Y, Zhou J, Winkler C, O'Brien SJ, Xu J, Mo Z, and Peng T
- Subjects
- Adenocarcinoma blood, Adenocarcinoma mortality, Adenocarcinoma secondary, China, Colorectal Neoplasms blood, Colorectal Neoplasms mortality, Colorectal Neoplasms pathology, Disease-Free Survival, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Kaplan-Meier Estimate, Lymphatic Metastasis, Male, Middle Aged, Risk Factors, Adenocarcinoma genetics, Carcinoembryonic Antigen blood, Colorectal Neoplasms genetics, Polymorphism, Single Nucleotide
- 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.
- Published
- 2014
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