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Variation in TP63 is associated with lung adenocarcinoma susceptibility in Japanese and Korean populations

Nature Genetics volume 42, pages 893–896 (2010)Cite this article

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Abstract

Lung cancer is the most common cause of death from cancer worldwide, and its incidence is increasing in East Asian and Western countries. To identify genetic factors that modify the risk of lung adenocarcinoma, we conducted a genome-wide association study in a Japanese cohort, with replication in two independent studies in Japanese and Korean individuals, in a total of 2,098 lung adenocarcinoma cases and 11,048 controls. The combined analyses identified two susceptibility loci for lung adenocarcinoma: TERT (rs2736100, combined P = 2.91 × 10−11, odds ratio (OR) = 1.27) and TP63 (rs10937405, combined P = 7.26 × 10−12, OR = 1.31). Fine mapping of the region containing TP63 showed that a SNP (rs4488809) in intron 1 of TP63 showed the most significant association. Our results suggest that genetic variation in TP63 may influence susceptibility to lung adenocarcinoma in East Asian populations.

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Figure 1: Case-control association plots, LD map and genomic structure of the TP63 region in chromosome 3q28.

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Acknowledgements

We thank the staff of the Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN and the Human Genome Center, Institute of Medical Science, The University of Tokyo for their contribution to SNP genotyping. We also thank members of the BioBank Japan project, the Rotary Club of Osaka-Midosuji District 2660 Rotary International in Japan, and Research Institute and Hospital, National Cancer Center, Korea for supporting our study. Y.D. is a member of the Shiga Cancer Treatment Project supported by Shiga Prefecture (Japan). This work was conducted as a part of the BioBank Japan Project and supported by the Ministry of Education, Culture, Sports, Sciences and Technology of the Japanese government. Management of second replication samples in Korea was supported by grants 0710221 and 0940620 from the National Cancer Center, Korea.

Author information

Authors and Affiliations

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

    Daiki Miki, Yusuke Nakamura & Yataro Daigo

  2. Department of Medical Molecular Science, Hiroshima University, Hiroshima, Japan

    Daiki Miki & Kazuaki Chayama

  3. Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN, Yokohama, Japan

    Michiaki Kubo & Naoya Hosono

  4. Laboratory for Statistical Analysis, Center for Genomic Medicine, RIKEN, Yokohama, Japan

    Atsushi Takahashi & Naoyuki Kamatani

  5. Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Korea.,

    Kyong-Ah Yoon, Jeongseon Kim, Geon Kook Lee, Jae Ill Zo & Jin Soo Lee

  6. Laboratory for Medical Informatics, Center for Genomic Medicine, RIKEN, Yokohama, Japan

    Takashi Morizono & Tatsuhiko Tsunoda

  7. Division of Molecular Carcinogenesis, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Takashi Takahashi

  8. Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan

    Johji Inazawa

  9. Department of Medical Oncology, Shiga University of Medical Science, Otsu, Japan

    Yataro Daigo

  10. Cancer Center, Shiga University of Medical Science Hospital, Otsu, Japan

    Yataro Daigo

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  1. Daiki Miki
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Contributions

Y.N. conceived the study; D.M., M.K., Y.N. and Y.D. designed the study; D.M., N.H., M.K. and Y.D. performed genotyping; D.M., M.K., Y.N. and Y.D. wrote the manuscript; A.T., T.M., T. Tsunoda and N.K. performed data analysis at the genome-wide phase; Y.N. and M.K. managed DNA samples belong to BioBank Japan; K.-A.Y., J.K., G.-K.L., J.I.Z. and J.S.L. managed second replication samples in Korea; D.M. and Y.D. summarized the results; Y.N., T. Takahashi, K.C., J.I. and Y.D. obtained funding for the study.

Corresponding author

Correspondence to Yataro Daigo.

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The authors declare no competing financial interests.

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Miki, D., Kubo, M., Takahashi, A. et al. Variation in TP63 is associated with lung adenocarcinoma susceptibility in Japanese and Korean populations. Nat Genet 42, 893–896 (2010). https://doi.org/10.1038/ng.667

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