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Association between UGT1A1*28*28 genotype and lung cancer in the Japanese population

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Abstract

Background

Lung cancer is the leading cause of cancer death and is closely linked to tobacco smoking. Genetic polymorphisms in genes that encode enzymes involved in metabolizing tobacco carcinogens could affect an individual’s risk for lung cancer. While polymorphism of UDP-glucuronosyltransferase1A1 (UGT1A1) is involved in detoxification of benzo(a)pyrene-7,8-dihydrodiol(–), a major tobacco carcinogen, the association between UGT1A1 genotype and lung cancer has not been examined.

Methods

We retrieved the clinical data of 5,285 patients who underwent systemic chemotherapy at Kyoto University Hospital. A total of 765 patients (194 lung cancer patients and 671 patients with other malignancies) with UGT1A1 genotyping data were included in this analysis. We used logistic regression with recessive, dominant, and additive models to identify differences in genotype frequencies between lung cancer and other malignancies.

Results

In the recessive model, UGT1A1*28*28 genotype was significantly associated with lung cancer compared to other malignancies (odds ratio 5.3, P = 0.0083). Among lung cancer patients with a smoking history, squamous cell carcinoma was significantly predominant in patients with UGT1A1*28*28 compared to those with other UGT1A1 genotypes (P = 0.024).

Conclusion

This is the first study to demonstrate a significant association between the homozygous UGT1A1*28 genotype and lung cancer.

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Acknowledgements

The authors express their gratitude to Dr. Masahide Onoue, Mr. Yasuaki Ikemi, Mr. Naoya Ishibashi and all the staff in the Department of Pharmacy, Kyoto University Hospital for UGT1A1 genotyping. This research was partially supported by a grant from the Practical Research for Innovative Cancer Control from the Japan Agency for Medical Research and Development.

Author information

Authors and Affiliations

  1. Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, Kyoto, 606-8507, Japan

    Yoshitaka Nishikawa, Masashi Kanai, Yu Uneno, Daisuke Yamaguchi, Yukiko Mori, Shigemi Matsumoto & Manabu Muto

  2. Department of Clinical Oncology, Pharmacogenomics, and Palliative Medicine, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

    Masashi Kanai & Yukiko Mori

  3. Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, 53 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

    Maiko Narahara

  4. Department of Human Genetics, McGill University, 740 Dr. Penfield Avenue, Montréal, H3A 0G1, Canada

    Maiko Narahara

  5. Department of Clinical System Onco-Informatics, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

    Akiko Tamon, J. B. Brown, Kei Taneishi, Masahiko Nakatsui & Yasushi Okuno

  6. Center for Medical Education, Graduate School of Medicine, Kyoto University, Konoemachi Med Bldg E, Sakyo-ku, Kyoto, 606-8501, Japan

    J. B. Brown

  7. RIKEN Advanced Institute for Computational Science, 7-1-26 Minatojima-minami-machi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan

    Kei Taneishi & Yasushi Okuno

  8. Division of Medical Information Technology and Administration Planning, Kyoto University Hospital, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

    Kazuya Okamoto

  9. Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

    Teruko Tomono

Authors
  1. Yoshitaka Nishikawa
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  2. Masashi Kanai
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  3. Maiko Narahara
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  4. Akiko Tamon
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  8. Kazuya Okamoto
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  9. Yu Uneno
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  10. Daisuke Yamaguchi
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  12. Yukiko Mori
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  13. Shigemi Matsumoto
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  14. Yasushi Okuno
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  15. Manabu Muto
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Corresponding author

Correspondence to Manabu Muto.

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Conflict of interest

Dr. Narahara received research funding from Toyobo Biotechnology Foundation. Dr. Muto received research funding from Taiho Pharmaceutical and Mitsui Knowledge Industry. No other potential conflict of interest relevant to this article was reported.

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Nishikawa, Y., Kanai, M., Narahara, M. et al. Association between UGT1A1*28*28 genotype and lung cancer in the Japanese population. Int J Clin Oncol 22, 269–273 (2017). https://doi.org/10.1007/s10147-016-1061-2

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  • DOI: https://doi.org/10.1007/s10147-016-1061-2

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