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A myeloperoxidase polymorphism associated with reduced risk of lung cancer
Matthew B Schabath1, Margaret R Spitz, Waun K Hong
1Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Box 189, 1515 Holcombe Blvd, Houston, TX 77030, USA.
Abstract:
Myeloperoxidase (MPO) is a metabolic/oxidative enzyme found in neutrophils and monocytes that contributes to pulmonary carcinogenesis through activation of specific procarcinogens including benzo[a]pyrene intermediates, 4-aminobiphenyl and the arylamines. There is a G-->A polymorphism located in the 5' untranslated region of the MPO gene that may be responsible for reduced transcriptional activity due to the decreased binding affinity for the SP1 transcription factor. Individuals with one or two copies of the A-allele may be afforded protection due to decreased transcriptional activity of MPO and subsequent decreased metabolic activation of procarcinogens. Previous studies have reported a range of protective effects in different ethnic populations. We employed a restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) assay to identify the MPO genotypes in 375 lung cancer cases and 378 healthy controls, all of whom were Caucasian. Our results demonstrate a reduced risk of lung cancer when the A-allele genotypes (G/A+A/A) were combined (odds ratio (OR)=0.66; 95% confidence interval (CI) 0.49-0.90). We also noted a protective effect (OR=0.63; 95% CI 0.45-0.87) in ever smokers with the A-allele genotypes which was not evident in never smokers (OR=1.14; 95% CI 0.42-3.11). We observed an incremental decrease in the protective effects as cigarette pack-years increased. Thus, lightest smokers were provided the greatest protection. When the data were stratified by gender, there was a statistically significant reduced risk of lung cancer among men (OR=0.55; 95% CI 0.36-0.84), but not among women (OR=0.81; 95% CI 0.55-1.26) for the A-allele genotypes. Lastly, an age effect was evident only in men but not women. The protective effects of the A-allele genotypes decreased with increasing age. This report provides further support for the hypothesis that a single nucleotide polymorphism in the MPO gene is a protective factor in lung cancer carcinogenesis.
Insights
A specific gene variant (A-allele) in the myeloperoxidase (MPO) gene is linked to a reduced risk of lung cancer, particularly in Caucasian men and light smokers. This MPO polymorphism may offer protection by decreasing procarcinogen activation.
Area of Science:
- Genetics and Genomics
- Cancer Research
- Molecular Biology
Background:
- Myeloperoxidase (MPO) is an enzyme involved in activating procarcinogens, contributing to lung cancer development.
- A G-to-A polymorphism in the MPO gene's 5' untranslated region may reduce its transcriptional activity.
- Previous studies suggest varying protective effects of this MPO polymorphism across different ethnic groups.
Purpose of the Study:
- To investigate the association between the MPO gene polymorphism and lung cancer risk in a Caucasian population.
- To determine if the MPO A-allele influences lung cancer risk based on smoking status, gender, and age.
Main Methods:
- A restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) assay was used to genotype MPO in 375 lung cancer cases and 378 healthy controls.
- Genotypes were analyzed for association with lung cancer risk, considering smoking history, gender, and age.
Main Results:
- Individuals with A-allele genotypes (G/A + A/A) showed a reduced risk of lung cancer (OR=0.66).
- A significant protective effect was observed in ever smokers (OR=0.63), especially in men (OR=0.55), with decreasing protection correlating with increased smoking pack-years and age.
- No significant protective effect was found in never smokers (OR=1.14) or women (OR=0.81).
Conclusions:
- The MPO gene A-allele polymorphism is associated with a decreased risk of lung cancer in Caucasians.
- This protective effect is more pronounced in men, light smokers, and appears to diminish with heavier smoking and increasing age.
- The findings support the hypothesis that MPO genetic variation plays a role in lung cancer susceptibility.