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.
journal_name
Lungjournal_title
Lungauthors
Murakami A,Fujimori Y,Yoshikawa Y,Yamada S,Tamura K,Hirayama N,Terada T,Kuribayashi K,Tabata C,Fukuoka K,Tamaoki T,Nakano Tdoi
10.1007/s00408-012-9371-2subject
Has Abstractpub_date
2012-06-01 00:00:00pages
333-7issue
3eissn
0341-2040issn
1432-1750journal_volume
190pub_type
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