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Point: myeloperoxidase -463G --> a polymorphism and lung cancer risk
Anne Feyler1, Anu Voho, Christine Bouchardy
1Unit of Cancer Epidemiology (INSERM U521), Gustave-Roussy Institute, 94805 Villejuif, France.
Abstract:
Myeloperoxidase (MPO) is released from neutrophils in lung tissue in response to exposure to various pulmonary insults, including tobacco smoking. This enzyme is involved in the activation of an intermediate metabolite of benzo(a)pyrene to the highly reactive benzo(a)pyrene diol epoxide. A (-463)G --> A polymorphism in the promoter region of the MPO gene has been identified. The A allele is associated with a decreased transcriptional activity attributable to the disruption of a SP1-binding site. We therefore examined whether carriers of the A allele may be at reduced risk of lung cancer in a case-control study of 150 cases and 172 control individuals, all Caucasian smokers. Relative to subjects with the MPO G/G genotype, a significant decreased risk of lung cancer was found for carriers of the G/A genotype [odds ratio (OR) = 0.5, 95% confidence interval (CI): 0.29-0.88]. A reduction in risk, although not statistically significant, was also observed for subjects with the A/A genotype (OR = 0.84, 95% CI: 0.31-2.32). The lung cancer risk for carriers of one or two copies of the A allele was 0.55 (95% CI: 0.33-0.93). Because of the low prevalence of the A/A genotype, we also performed a meta-analysis of 2686 lung cancer cases and 3325 controls. The summary OR suggested a slight protective effect of the A/A genotype (OR = 0.86, 95% CI: 0.67-1.1), but this finding was strongly influenced by the results of a single large study. The meta-analysis restricted to studies comprising a homogeneous set yielded an OR of 0.68 (95% CI: 0.5-0.93). However, because of the heterogeneity in individual study results, additional large case-control studies are warranted to provide a more definitive conclusion.
Insights
Smokers with a specific MPO gene variant (A allele) show a reduced risk of lung cancer. This finding suggests a potential protective effect of this MPO genotype against smoking-related lung cancer.
Area of Science:
- Genetics
- Oncology
- Environmental Health
Background:
- Myeloperoxidase (MPO) is released from neutrophils in lung tissue following exposure to pulmonary insults like tobacco smoke.
- MPO activates benzo(a)pyrene metabolites into reactive compounds implicated in lung cancer.
- A polymorphism in the MPO gene promoter (G --> A at -463) affects transcriptional activity.
Purpose of the Study:
- To investigate the association between the MPO gene polymorphism and lung cancer risk in Caucasian smokers.
- To determine if carriers of the MPO A allele have a reduced risk of developing lung cancer.
Main Methods:
- A case-control study was conducted with 150 lung cancer cases and 172 controls, all Caucasian smokers.
- Genotyping for the MPO (-463)G --> A polymorphism was performed.
- A meta-analysis of published data was conducted, including 2686 cases and 3325 controls.
Main Results:
- Carriers of the MPO G/A genotype had a significantly decreased risk of lung cancer (OR = 0.5).
- A non-significant risk reduction was observed for the A/A genotype (OR = 0.84).
- Combined analysis showed a reduced risk for carriers of the A allele (OR = 0.55).
- Meta-analysis suggested a protective effect for the A/A genotype (OR = 0.86), but heterogeneity was noted.
Conclusions:
- The MPO A allele may confer a reduced risk of lung cancer in Caucasian smokers.
- Further large-scale studies are needed to confirm these findings due to observed heterogeneity.