Heme oxygenase-1 promoter polymorphism is associated with risk of malignant mesothelioma

Our plain-English summary of Heme oxygenase-1 promoter polymorphism is associated with risk of malignant mesothelioma, by A. Murakami, Y. Fujimori, Y. Yoshikawa, et al (Lung, 2012).

The study

• Authors: A. Murakami, Y. Fujimori, Y. Yoshikawa, S. Yamada, K. Tamura, N. Hirayama, T. Terada, K. Kuribayashi, C. Tabata, K. Fukuoka, T. Tamaoki, T. Nakano
• Journal: Lung
• Published: 2012;190(3):333-7
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

In plain English

This Japanese study compared the genes of 78 asbestos-exposed people with malignant mesothelioma and 44 asbestos-exposed people without it. The patients were diagnosed at Hyogo College of Medicine Hospital between March 2000 and August 2007. From blood samples, the authors measured a repeating DNA sequence, called (GT)n repeats, in the control region of the heme oxygenase-1 (HO-1) gene. This gene makes an enzyme that protects against oxidative stress. They grouped gene copies as short (fewer than 24 repeats) or long (24 or more). Long copies made up 78.8% of 156 gene copies in the mesothelioma group and 64.8% of 88 copies in the comparison group (odds ratio 2.027, 95% confidence interval 1.132 to 3.628). At least one long copy was found in 97.5% of patients and 86.4% of comparison subjects (odds ratio 6.00, 95% confidence interval 1.155 to 31.149). Smoking did not differ significantly between the groups. The authors concluded that long repeats are associated with a higher risk of malignant mesothelioma in the Japanese population. They noted that cancer has many causes and that larger studies in other ethnic groups are needed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Case-control genetic association study comparing asbestos-exposed subjects with and without mesothelioma, using PCR-based genotyping of the HO-1 gene promoter
• Who was studied: 122 asbestos-exposed subjects in Japan: 78 with malignant mesothelioma, diagnosed at Hyogo College of Medicine Hospital (Nishinomiya, Hyogo) between March 2000 and August 2007 and confirmed on pleural biopsy, and 44 without mesothelioma
• Exposure: Asbestos exposure at the workplace, home and other places was recorded for all subjects. Fiber types, jobs and doses were not reported. The factor studied was the length of the (GT)n repeat in the HO-1 gene promoter: short (fewer than 24 repeats) or long (24 or more).
• Main results:
  • In all subjects the number of (GT)n repeats ranged from 16 to 38, with peaks at 23 and 30 repeats.
  • Long alleles made up 123 of 156 alleles (78.8%) in subjects with mesothelioma and 57 of 88 alleles (64.8%) in subjects without mesothelioma (p = 0.016, OR = 2.027, 95% CI = 1.132–3.628).
  • Carriers of at least one long allele (L/L or L/S) were 76 (97.5%) of subjects with mesothelioma and 38 (86.4%) of subjects without mesothelioma (p = 0.025, OR = 6.00, 95% CI 1.155–31.149).
  • Comparing the L/L genotype with the S/S genotype gave p = 0.015 and OR = 7.421 (95% CI 1.373–40.086). L/L was seen in 47 (60.3%) of subjects with mesothelioma and 19 (43.2%) of those without. S/S was seen in 2 (2.5%) and 6 (13.6%) respectively.
  • The two groups did not differ significantly in smoking habits or mean Brinkman's index for smokers (791.9 without mesothelioma vs 804.2 with mesothelioma). They also did not differ significantly in emphysema, cardiovascular disease, hypertension or diabetes.
• The authors' conclusion: The authors concluded that the study suggests long (GT)n repeats in the HO-1 gene promoter are associated with a higher risk of malignant mesothelioma in the Japanese population.
• Limitations the authors state:
  • The authors stated that cancer development is multifactorial and cannot be defined by a single-gene polymorphism, and that further studies with larger numbers of samples from different ethnicities are needed.
  • The authors stated that they lacked sufficient data on how the (GT)n repeats are distributed in their ethnic population, so a more definitive Bayesian analysis was not yet possible.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Serosal Surface, Asbestos Exposure, Oxidative Stress, Mesothelioma.

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