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

Journal name:
Nature Genetics
Volume:
43,
Pages:
1215–1218
Year published:
DOI:
doi:10.1038/ng.978
Received
Accepted
Published online

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.

At a glance

Figures

  1. Plot of the genome-wide P values of association with non-cardia gastric cancer in the Han Chinese population.
    Figure 1: Plot of the genome-wide P values of association with non-cardia gastric cancer in the Han Chinese population.

    Scatter plot of P values in −log10 scale from the additive model in 1,006 cases and 2,273 controls. Blue horizontal line, P = 1.0 × 10−5; red horizontal line, P = 1.0 × 10−7; green dots, rs9841504 and rs13361707.

  2. Regional plot of the two new susceptibility loci for non-cardia gastric cancer.
    Figure 2: Regional plot of the two new susceptibility loci for non-cardia gastric cancer.

    (a) 5p13.1 and (b) 3q13.31. Association results (−log10 P) of both genotyped (filled circle) and imputed (open diamond) SNPs in the GWAS samples are shown for SNPs in the regions 400 kb upstream and downstream of the marker SNPs. The marker SNPs are shown in purple, and the r2 values of the remaining SNPs are indicated by color. The genes within the region are annotated and shown as arrows.

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Author information

  1. These authors contributed equally to this work.

    • Yongyong Shi,
    • Zhibin Hu &
    • Chen Wu

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

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.

Competing financial interests

The authors declare no competing financial interests.

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