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A genome-wide association study identifies two new susceptibility loci for lung adenocarcinoma in the Japanese population

Nature Genetics volume 44, pages 900–903 (2012)Cite this article

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Abstract

Lung adenocarcinoma is the most common histological type of lung cancer, and its incidence is increasing worldwide. To identify genetic factors influencing risk of lung adenocarcinoma, we conducted a genome-wide association study and two validation studies in the Japanese population comprising a total of 6,029 individuals with lung adenocarcinoma (cases) and 13,535 controls. We confirmed two previously reported risk loci, 5p15.33 (rs2853677, Pcombined = 2.8 × 10−40, odds ratio (OR) = 1.41) and 3q28 (rs10937405, Pcombined = 6.9 × 10−17, OR = 1.25), and identified two new susceptibility loci, 17q24.3 (rs7216064, Pcombined = 7.4 × 10−11, OR = 1.20) and 6p21.3 (rs3817963, Pcombined = 2.7 × 10−10, OR = 1.18). These data provide further evidence supporting a role for genetic susceptibility in the development of lung adenocarcinoma.

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Figure 1: Regional plots of the identified marker SNPs.

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Acknowledgements

We thank all of the subjects for participating in the study, and we also thank the collaborating physicians for assisting with sample collection. We are grateful to the members of BioBank Japan, the National Cancer Center Biobank and the Rotary Club of Osaka-Midosuji District 2660 Rotary International in Japan for supporting our study. We thank Y. Aoi, T. Odaka, M. Okuyama, H. Totsuka, S. Chiku, A. Kuchiba and the technical staff of the Center for Genome Medicine, National Cancer Center Research Institute, for providing technical and methodological assistance. We also thank H. Hirose of Health Center, Keio University and D. Saito of National Cancer Center Hospital (present affiliation: Nihonbashi Daizo Clinic) for DNA samples of control subjects. This work was supported in part by Grants-in-Aid from the Ministry of Health, Labor and Welfare for Research on Applying Health Technology and for the 3rd-term Comprehensive 10-year Strategy for Cancer Control; from the Ministry of Education, Culture, Sports, Science and Technology of Japan for Scientific Research on Innovative Areas (22131006); from the Japan Society for the Promotion of Science for Research Activity Start-up (23800073) and for Young Scientists (B) (24790340); and by the National Cancer Center Research and Development Fund. This work was also conducted as a part of the BioBank Japan Project supported by the Ministry of Education, Culture, Sports, Science and Technology, Japan. The National Cancer Center Biobank is supported by the National Cancer Center Research and Development Fund, Japan.

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Author notes

  1. Hideo Kunitoh

    Present address: Present address: Department of Respiratory Medicine, Mitsui Memorial Hospital, Tokyo, Japan.,

Authors and Affiliations

  1. Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan

    Kouya Shiraishi, Yoko Shimada & Takashi Kohno

  2. Division of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan

    Hideo Kunitoh

  3. Department of Medical Oncology, Shiga University of Medical Science, Shiga, Japan

    Yataro Daigo

  4. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan

    Yataro Daigo & Yusuke Nakamura

  5. Laboratory for Statistical Analysis, Center for Genomic Medicine, RIKEN, Kanagawa, Japan

    Atsushi Takahashi & Naoyuki Kamatani

  6. Thoracic Oncology Division, National Cancer Center Hospital East, Chiba, Japan

    Koichi Goto

  7. Division of Genetics, National Cancer Center Research Institute, Tokyo, Japan

    Hiromi Sakamoto, Sumiko Ohnami & Teruhiko Yoshida

  8. Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN, Kanagawa, Japan

    Kyota Ashikawa & Michiaki Kubo

  9. Statistical Genetics Analysis Division, StaGen Co. Ltd, Tokyo, Japan

    Akira Saito

  10. Division of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan

    Shun-ichi Watanabe

  11. Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan

    Koji Tsuta

  12. Division of Multistep Carcinogenesis, National Cancer Center Research Institute, Tokyo, Japan

    Jun Yokota

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  1. Kouya Shiraishi
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Contributions

K.S., J.Y., M.K. and T.K. designed the study. A.T., K.A., S.O., N.K. and A.S. analyzed the GWAS and replication study. H.S., Y.S., T.Y. and K.S. performed the genotyping for the GWAS and the replication study. H.K., K.G., S.W. and K.T. recruited subjects and participated in diagnostic evaluations. K.S. and T.K. wrote the manuscript. M.K., Y.D., T.Y. and Y.N. contributed to the overall GWAS design.

Corresponding author

Correspondence to Takashi Kohno.

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The authors declare no competing financial interests.

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Supplementary Note, Supplementary Figures 1 and 2 and Supplementary Tables 1–8. (PDF 2431 kb)

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Shiraishi, K., Kunitoh, H., Daigo, Y. et al. A genome-wide association study identifies two new susceptibility loci for lung adenocarcinoma in the Japanese population. Nat Genet 44, 900–903 (2012). https://doi.org/10.1038/ng.2353

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