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- Title
Heme Oxygenase-1 Promoter Polymorphism is Associated with Risk of Malignant Mesothelioma.
- Authors
Murakami, Aki; Fujimori, Yoshihiro; Yoshikawa, Yoshie; Yamada, Shusai; Tamura, Kunihiro; Hirayama, Noriko; Terada, Takayuki; Kuribayashi, Kozo; Tabata, Chiharu; Fukuoka, Kazuya; Tamaoki, Tomoko; Nakano, Takashi
- 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.
- Subjects
HEME oxygenase; MESOTHELIOMA; OXIDATIVE stress; ASBESTOS &; health; DISEASE susceptibility
- Publication
Lung, 2012, Vol 190, Issue 3, p333
- ISSN
0341-2040
- Publication type
Article
- DOI
10.1007/s00408-012-9371-2