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Myeloperoxidase promotor polymorphism and risk of hepatoblastoma
Samart Pakakasama1, Tina T-L Chen, William Frawley
1Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390-8593, USA.
Abstract:
Myeloperoxidase (MPO) is a major enzyme found in neutrophils. Oxidation by MPO produces free radicals that demonstrate genotoxic properties. A polymorphism (G to A) within the promotor region of the MPO gene reduces transcription and expression. This polymorphism is associated with a protective effect against some cancers in adults including lung cancer. The objective of our study was to investigate the effect of this MPO polymorphism on the risk of hepatoblastoma, the most common cancer of the liver in childhood. By using PCR-SSCP, we determined the genotype at this polymorphism in 48 cases of Caucasian children with hepatoblastoma and 180 normal controls. Genotypes were confirmed by a second method using Aci I restriction enzyme restriction. We found that A allele was associated with reduced risk of hepatoblastoma of 50% (OR, 0.51; 95%CI, 0.27-0.93) and G/A or A/A genotype reduced the risk by 56% (OR, 0.44; 95%CI, 0.21-0.90). Our data suggest that A allele is a protective factor with regard to the risk of hepatoblastoma, perhaps by altering genotoxic properties of xenobiotic substances which may act as carcinogens.
Insights
The MPO A allele may protect children against hepatoblastoma, a common childhood liver cancer. This genetic variation in myeloperoxidase (MPO) reduces cancer risk by approximately 50%.
Area of Science:
- Genetics
- Oncology
- Biochemistry
Background:
- Myeloperoxidase (MPO) is a neutrophil enzyme.
- MPO-derived oxidants possess genotoxic properties.
- A specific MPO gene promoter polymorphism (G to A) influences enzyme expression and is linked to reduced adult cancer risk.
Purpose of the Study:
- To investigate the association between the MPO gene polymorphism and the risk of childhood hepatoblastoma.
- To determine if the MPO A allele confers a protective effect against hepatoblastoma development.
Main Methods:
- Genotyping of the MPO G-to-A promoter polymorphism using PCR-SSCP in 48 hepatoblastoma cases and 180 controls.
- Confirmation of genotypes using Aci I restriction enzyme digestion.
- Statistical analysis to assess the association between MPO genotypes and hepatoblastoma risk.
Main Results:
- The MPO A allele was associated with a 50% reduction in hepatoblastoma risk (OR, 0.51; 95%CI, 0.27-0.93).
- Individuals with the G/A or A/A genotype showed a 56% decreased risk (OR, 0.44; 95%CI, 0.21-0.90).
Conclusions:
- The MPO A allele appears to be a protective factor against hepatoblastoma in childhood.
- This protective effect may stem from altered genotoxic properties of xenobiotics, potentially reducing carcinogen-induced damage.