title: A genome wide association study of genetic loci that influence tumour biomarkers cancer antigen 19-9, carcinoembryonic antigen and α fetoprotein and their associations with cancer risk.
abstract: OBJECTIVE
  Tumour biomarkers are used as indicators for cancer screening and as predictors for therapeutic responses and prognoses in cancer patients. We aimed to identify genetic loci that influence concentrations of cancer antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA) and α fetoprotein (AFP), and investigated the associations between the significant single nucleotide polymorphisms (SNPs) with risks of oesophageal squamous cell (OSCC), pancreatic and hepatocellular cancers.
  
  
  METHODS
  We carried out a genome wide association study on plasma CA19-9, CEA and AFP concentrations in 3451 healthy Han Chinese and validated the results in 10 326 individuals. Significant SNPs were further investigated in three case control studies (2031 OSCC cases and 2044 controls; 981 pancreatic cancer cases and 1991 controls; and 348 hepatocellular cancer cases and 359 controls).
  
  
  RESULTS
  The analyses showed association peaks on three genetic loci for CA19-9 (FUT6-FUT3 at 19p13.3, FUT2-CA11 at 19q13.3 and B3GNT3 at 19p13.1; p=1.16×10(-13)-3.30×10(-290)); four for CEA (ABO at 9q34.2, FUT6 at 19p13.3, FUT2 at 19q13.3 and FAM3B at 21q22.3; p=3.33×10(-22)-5.81×10(-209)); and two for AFP (AFP at 4q11-q13 and HISPPD2A at 15q15.3; p=3.27×10(-18) and 1.28×10(-14)). These explained 17.14% of the variations in CA19-9, 8.95% in CEA and 0.57% in AFP concentrations. Significant ABO variants were also associated with risk of OSCC and pancreatic cancers, and AFP variants with risk of hepatocellular cancer (p<0.05).
  
  
  CONCLUSIONS
  This study identified several loci associated with CA19-9, CEA and AFP concentrations. The ABO variants were associated with risk of OSCC and pancreatic cancers and AFP variants with risk of hepatocellular cancer.
authors.affiliation: MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, , Wuhan, Hubei, China.
authors.forename: Meian
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authors.forename: Yanling
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authors.forename: Mingjian
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authors.forename: Sha
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authors.lastname: Tao
authors.forename: Yuanfeng
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authors.forename: Yi
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authors.forename: Junjie
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authors.forename: Dongfeng
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authors.lastname: Li
authors.forename: Seong-Tae
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authors.lastname: Kim
authors.forename: Shijun
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authors.lastname: Zhang
authors.forename: Hongxing
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authors.lastname: Zhang
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authors.forename: Lixuan
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authors.lastname: Gui
authors.forename: Youjie
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authors.lastname: Wang
authors.forename: Sheng
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authors.lastname: Wei
authors.forename: Feng
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authors.lastname: Wang
authors.forename: Weimin
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authors.lastname: Fang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liang
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhai
authors.forename: Weihong
authors.initials: W
authors.lastname: Chen
authors.forename: Xiaoping
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authors.lastname: Miao
authors.forename: Gangqiao
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authors.lastname: Zhou
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.forename: Dongxin
authors.initials: D
authors.lastname: Lin
authors.forename: Zengnan
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authors.forename: Tangchun
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mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D014408:Biomarkers, Tumor / Q000235:genetics*; D018395:CA-19-9 Antigen / Q000235:genetics; D002272:Carcinoembryonic Antigen / Q000235:genetics; D002277:Carcinoma / Q000208:ethnology / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000208:ethnology / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000208:ethnology / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D004938:Esophageal Neoplasms / Q000208:ethnology / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D016014:Linear Models; D008113:Liver Neoplasms / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D000509:alpha-Fetoproteins / Q000235:genetics
chemical_list: C097353:AFP protein, human; D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D002272:Carcinoembryonic Antigen; D000509:alpha-Fetoproteins
keywords: Cancer Genetics; Cancer Susceptibility