title: Genetic variations affecting serum carcinoembryonic antigen levels and status of regional lymph nodes in patients with sporadic colorectal cancer from Southern China.
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.
  
  
  RESULTS
  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.
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Anal and colorectal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
authors.forename: Weizhong
authors.initials: W
authors.lastname: Tang
authors.affiliation: Department of Anal and colorectal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
authors.forename: Tiqiang
authors.initials: T
authors.lastname: Huang
authors.affiliation: Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Tan
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
authors.forename: Xue
authors.initials: X
authors.lastname: Qin
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.affiliation: Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
authors.forename: Shijun
authors.initials: S
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Linjian
authors.initials: L
authors.lastname: Mo
authors.affiliation: Medical Examination Center, Fangchenggang First People's Hospital, Fangchenggang, Guangxi, People's Republic of China.
authors.forename: Zhenjia
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Medical Examination Center, Fangchenggang First People's Hospital, Fangchenggang, Guangxi, People's Republic of China.
authors.forename: Deyi
authors.initials: D
authors.lastname: Shi
authors.affiliation: Medical Examination Center, Guigang First People's Hospital, Guigang, Guangxi, People's Republic of China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Medical Examination Center, Yulin First People's Hospital, Yulin, Guangxi, People's Republic of China.
authors.forename: Yingyong
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Department of Hematology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
authors.forename: Jicheng
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Molecular Genetics Epidemiology Sec., Frederick Nat. Lab for Cancer Research, National Cancer Institute, NIH, Frederick, Maryland, United States of America.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Winkler
authors.affiliation: 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.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: O'Brien
authors.affiliation: 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.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Zengnan
authors.initials: Z
authors.lastname: Mo
authors.affiliation: 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.
authors.forename: Tao
authors.initials: T
authors.lastname: Peng
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D002272:Carcinoembryonic Antigen / Q000097:blood*; D002681:China; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D002272:Carcinoembryonic Antigen