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Heme Oxygenase-1 Promoter Polymorphism is Associated with Risk of Malignant Mesothelioma

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Abstract

Background

Malignant mesothelioma is an aggressive tumor of serosal surfaces that is closely associated with asbestos exposure which induces oxidative stress. Heme oxygenase (HO)-1, a rate-limiting enzyme of heme degradation, plays a protective role against oxidative stress. The HO-1 gene promoter carries (GT)n repeats whose number is inversely related to transcriptional activity of the HO-1 gene.

Methods

To investigate the relationship between the length polymorphism of (GT)n repeats and mesothelioma susceptibility, we analyzed the HO-1 promoter in 44 asbestos-exposed subjects without mesothelioma and 78 asbestos-exposed subjects with mesothelioma using PCR-based genotyping.

Results

The number of repeats ranged from 16 to 38, with two peaks at 23 and 30 repeats. Polymorphisms of (GT)n repeats were grouped into two classes of alleles, short (S) (<24) and long (L) (≥24), and three genotypes: L/L, L/S, and S/S. The proportions of allele frequencies in class L as well as genotypic frequencies of L allele carriers (L/L and L/S) were significantly higher in the asbestos-exposed subjects with mesothelioma than in those without mesothelioma.

Conclusion

The findings of this study suggest that long (GT)n repeats in the HO-1 gene promoter are associated with a higher risk of malignant mesothelioma in the Japanese population.

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Acknowledgments

We are grateful to Dr. Takashi Daimon (Department of Mathematics, Hyogo College of Medicine) for performing the statistical analysis. This study was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science, and in part by the Special Coordination Funds for Science and Technology from Japan Science and Technology Agency.

Conflict of interest

The authors have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Division of Respiratory Medicine, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan

    Aki Murakami, Shusai Yamada, Kunihiro Tamura, Noriko Hirayama, Takayuki Terada, Kozo Kuribayashi, Chiharu Tabata, Kazuya Fukuoka & Takashi Nakano

  2. Hyogo College of Medicine, Cancer Center, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan

    Yoshihiro Fujimori

  3. Department of Genetics, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan

    Yoshie Yoshikawa & Tomoko Tamaoki

Authors
  1. Aki Murakami
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  2. Yoshihiro Fujimori
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  3. Yoshie Yoshikawa
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  4. Shusai Yamada
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Correspondence to Yoshihiro Fujimori.

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Murakami, A., Fujimori, Y., Yoshikawa, Y. et al. Heme Oxygenase-1 Promoter Polymorphism is Associated with Risk of Malignant Mesothelioma. Lung 190, 333–337 (2012). https://doi.org/10.1007/s00408-012-9371-2

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  • DOI: https://doi.org/10.1007/s00408-012-9371-2

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