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Tumour biomarkers
Original article
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
  1. Meian He1,2,
  2. Chen Wu3,
  3. Jianfeng Xu2,4,5,6,
  4. Huan Guo1,
  5. Handong Yang7,
  6. Xiaomin Zhang1,8,
  7. Jielin Sun9,
  8. Dianke Yu3,
  9. Li Zhou1,
  10. Tao Peng10,11,
  11. Yunfeng He1,
  12. Yong Gao2,6,
  13. Jing Yuan1,
  14. Qifei Deng1,
  15. Xiayun Dai1,
  16. Aihua Tan2,
  17. Yingying Feng1,
  18. Haiying Zhang12,
  19. Xinwen Min7,
  20. Xiaobo Yang12,
  21. Jiang Zhu7,
  22. Kan Zhai3,
  23. Jiang Chang3,
  24. Xue Qin13,
  25. Wen Tan3,
  26. Yanling Hu14,
  27. Mingjian Lang7,
  28. Sha Tao14,
  29. Yuanfeng Li15,
  30. Yi Li7,
  31. Junjie Feng9,
  32. Dongfeng Li7,
  33. Seong-Tae Kim9,
  34. Shijun Zhang2,
  35. Hongxing Zhang15,
  36. S Lilly Zheng9,
  37. Lixuan Gui1,
  38. Youjie Wang1,
  39. Sheng Wei1,
  40. Feng Wang1,
  41. Weimin Fang1,
  42. Yuan Liang1,
  43. Yun Zhai15,
  44. Weihong Chen1,
  45. Xiaoping Miao1,
  46. Gangqiao Zhou15,
  47. Frank B Hu8,
  48. Dongxin Lin3,
  49. Zengnan Mo2,
  50. Tangchun Wu1
  1. 1MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
  2. 2Institute of Urology and Nephrology, First Affiliated Hospital and Centre for Genomic and Personalised Medicine, Guangxi Medical University, Nanning, Guangxi, China
  3. 3State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
  4. 4Fudan University Institute of Urology, Huashan Hospital, and Fudan-VARI Centre for Genetic Epidemiology, School of Life Sciences, Fudan University, Shanghai, China
  5. 5Center for Genetic Epidemiology, Van Andel Research Institute, Grand Rapids, Michigan, USA
  6. 6Fudan-VARI Centre for Genetic Epidemiology, School of Life Sciences, Fudan University, Shanghai, China
  7. 7Department of Cardiology, Dongfeng Central Hospital, Dongfeng Motor Corporation and Hubei University of Medicine, Shiyan, Hubei, China
  8. 8Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
  9. 9Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
  10. 10Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
  11. 11Laboratory of Genomic Diversity, National Cancer Institute, NIH, Frederick, Maryland, USA
  12. 12Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
  13. 13Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
  14. 14Medical Scientific Research Centre, Guangxi Medical University, Nanning, Guangxi, China
  15. 15State Key Laboratory of Proteomics, Beijing Proteome Research Centre, Beijing Institute of Radiation Medicine, Beijing, China
  1. Correspondence to Dr T Wu, School of Public Health, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei 430030, China; wut{at}mails.tjmu.edu.cn

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.

Design 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.

  • Cancer Genetics
  • Cancer Susceptibility

https://doi.org/10.1136/gutjnl-2012-303434

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