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A genome-wide association study identifies new susceptibility loci for non-cardia gastric cancer at 3q13.31 and 5p13.1

Nature Genetics volume 43, pages 1215–1218 (2011)Cite this article

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Abstract

Gastric cancer, including the cardia and non-cardia types, is the second leading cause of cancer-related deaths worldwide. To identify genetic risk variants for non-cardia gastric cancer, we performed a genome-wide association study in 3,279 individuals (1,006 with non-cardia gastric cancer and 2,273 controls) of Chinese descent. We replicated significant associations in an additional 6,897 subjects (3,288 with non-cardia gastric cancer and 3,609 controls). We identified two new susceptibility loci for non-cardia gastric cancer at 5p13.1 (rs13361707 in the region including PTGER4 and PRKAA1; odds ratio (OR) = 1.41; P = 7.6 × 10−29) and 3q13.31 (rs9841504 in ZBTB20; OR = 0.76; P = 1.7 × 10−9). Imputation analyses also confirmed previously reported associations of rs2294008 and rs2976392 on 8q24, rs4072037 on 1q22 and rs13042395 on 20p13 with non-cardia gastric cancer susceptibility in the Han Chinese population.

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Figure 1: Plot of the genome-wide P values of association with non-cardia gastric cancer in the Han Chinese population.
Figure 2: Regional plot of the two new susceptibility loci for non-cardia gastric cancer.

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References

  1. Tran, G.D. et al. Prospective study of risk factors for esophageal and gastric cancers in the Linxian general population trial cohort in China. Int. J. Cancer 113, 456–463 (2005).

    Article  CAS  Google Scholar 

  2. Gammon, M.D. et al. Tobacco, alcohol, and socioeconomic status and adenocarcinomas of the esophagus and gastric cardia. J. Natl. Cancer Inst. 89, 1277–1284 (1997).

    Article  CAS  Google Scholar 

  3. Mayne, S.T. & Navarro, S.A. Diet, obesity and reflux in the etiology of adenocarcinomas of the esophagus and gastric cardia in humans. J. Nutr. 132, 3467S–3470S (2002).

    Article  CAS  Google Scholar 

  4. Peek, R.M. Jr. & Blaser, M.J. Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nat. Rev. Cancer 2, 28–37 (2002).

    Article  CAS  Google Scholar 

  5. Wang, L.D. et al. Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54. Nat. Genet. 42, 759–763 (2010).

    Article  CAS  Google Scholar 

  6. Abnet, C.C. et al. A shared susceptibility locus in PLCE1 at 10q23 for gastric adenocarcinoma and esophageal squamous cell carcinoma. Nat. Genet. 42, 764–767 (2010).

    Article  CAS  Google Scholar 

  7. Freedman, M.L. et al. Assessing the impact of population stratification on genetic association studies. Nat. Genet. 36, 388–393 (2004).

    Article  CAS  Google Scholar 

  8. Shackelford, D.B. & Shaw, R.J. The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat. Rev. Cancer 9, 563–575 (2009).

    Article  CAS  Google Scholar 

  9. Sugimoto, Y. & Narumiya, S. Prostaglandin E receptors. J. Biol. Chem. 282, 11613–11617 (2007).

    Article  CAS  Google Scholar 

  10. Kabashima, K. et al. Prostaglandin E2–EP4 signaling initiates skin immune responses by promoting migration and maturation of Langerhans cells. Nat. Med. 9, 744–749 (2003).

    Article  CAS  Google Scholar 

  11. Okuyama, T. et al. Activation of prostaglandin E2-receptor EP2 and EP4 pathways induces growth inhibition in human gastric carcinoma cell lines. J. Lab. Clin. Med. 140, 92–102 (2002).

    Article  CAS  Google Scholar 

  12. Libioulle, C. et al. Novel Crohn disease locus identified by genome-wide association maps to a gene desert on 5p13.1 and modulates expression of PTGER4. PLoS Genet. 3, e58 (2007).

    Article  Google Scholar 

  13. Xie, Z. et al. Zinc finger protein ZBTB20 is a key repressor of alpha-fetoprotein gene transcription in liver. Proc. Natl. Acad. Sci. USA 105, 10859–10864 (2008).

    Article  CAS  Google Scholar 

  14. Zhang, W. et al. Identification and characterization of DPZF, a novel human BTB/POZ zinc finger protein sharing homology to BCL-6. Biochem. Biophys. Res. Commun. 282, 1067–1073 (2001).

    Article  CAS  Google Scholar 

  15. Sakamoto, H. et al. Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer. Nat. Genet. 40, 730–740 (2008).

    Article  CAS  Google Scholar 

  16. Wu, C. et al. Two genetic variants in prostate stem cell antigen and gastric cancer susceptibility in a Chinese population. Mol. Carcinog. 48, 1131–1138 (2009).

    Article  CAS  Google Scholar 

  17. Lu, Y. et al. Genetic variation of PSCA gene is associated with the risk of both diffuse- and intestinal-type gastric cancer in a Chinese population. Int. J. Cancer 127, 2183–2189 (2010).

    Article  CAS  Google Scholar 

  18. Zhang, H. et al. Genetic variants at 1q22 and 10q23 reproducibly associated with gastric cancer susceptibility in a Chinese population. Carcinogenesis 32, 848–852 (2011).

    Article  CAS  Google Scholar 

  19. Purdue, M.P. et al. Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3. Nat. Genet. 43, 60–65 (2011).

    Article  CAS  Google Scholar 

  20. Price, A.L. et al. Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet. 38, 904–909 (2006).

    Article  CAS  Google Scholar 

  21. Purcell, S. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559–575 (2007).

    Article  CAS  Google Scholar 

  22. Higgins, J.P. & Thompson, S.G. Quantifying heterogeneity in a meta-analysis. Stat. Med. 21, 1539–1558 (2002).

    Article  Google Scholar 

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Acknowledgements

We thank all the study participants, research staff and students who took part in this work. Funding was provided by grants from the China National High-Tech Research and Development Program (2009AA022705, 2009AA022704 and 2009AA022701), the National Natural Science Foundation of China (30700684, 81130022, 30671814, 81001276, 81072380 and 31000553), the Jiangsu Natural Science Foundation (BK2008221), the Foundation for the Author of National Excellent Doctoral Dissertation (201081 and 201026), the Program for New Century Excellent Talents in University (NCET-09-0550 and NCET-10-0178) and the Priority Academic Program for the Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine).

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  1. Yongyong Shi, Zhibin Hu and Chen Wu: These authors contributed equally to this work.

Authors and Affiliations

  1. Bio-X Institutes, Ministry of Education Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai, China

    Yongyong Shi & Zhiqiang Li

  2. Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China

    Zhibin Hu, Juncheng Dai, Huizhang Li, Jing Dong, Feng Lu, Hanze Zhang, Lingmin Hu, Yue Jiang, Minjie Chu, Hongxia Ma, Jiaping Chen, Guangfu Jin & Hongbing Shen

  3. Section of Clinical Epidemiology, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China

    Zhibin Hu, Jiaping Chen, Guangfu Jin & Hongbing Shen

  4. State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China

    Zhibin Hu & Hongbing Shen

  5. Department of Etiology and Carcinogenesis, State Key Laboratory of Molecular Oncology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Chen Wu, Wen Tan & Dongxin Lin

  6. Department of Occupational Medicine and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing, China

    Meilin Wang & Zhengdong Zhang

  7. Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Xiaoping Miao & Tangchun Wu

  8. Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, Medical College, Soochow University, Suzhou, China

    Yifeng Zhou

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  1. Yongyong Shi
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Contributions

H.S. took full responsibility for the study, including study design, obtaining financial support, data interpretation and manuscript submission. D.L. and Y.S. co-directed the study, obtained financial support and were responsible for study design, the interpretation of results and writing the manuscript. Z.H. contributed financial support, performed overall project management, performed statistical analyses along with J. Dai and drafted the initial manuscript. H. Li, F.L., H.Z., L.H., Y.J., Z.L. and M.C. were responsible for sample processing and managed the genotyping data. M.W., Y.Z., H. Li, J. Dong, H. Ma, G.J., J.C. and Z.Z. were responsible for subject recruitment and sample preparation for the Jiangsu samples. C.W., X.M. and W.T. were responsible for subject recruitment and sample preparation for the Beijing samples and reviewed the manuscript. T.W. participated in the study design and reviewed the manuscript. All authors approved the final manuscript.

Corresponding authors

Correspondence to Yongyong Shi, Dongxin Lin or Hongbing Shen.

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The authors declare no competing financial interests.

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Shi, Y., Hu, Z., Wu, C. et al. A genome-wide association study identifies new susceptibility loci for non-cardia gastric cancer at 3q13.31 and 5p13.1. Nat Genet 43, 1215–1218 (2011). https://doi.org/10.1038/ng.978

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