Interactions between paraoxonase 1 genetic polymorphisms and smoking and their effects on oxidative stress and lung cancer risk in a Korean population.

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Oxidative Stress* ; Polymorphism, Single Nucleotide* ; Smoking*; Aryldialkylphosphatase/*genetics ; Lung Neoplasms/*genetics; Aged ; Cocarcinogenesis ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Republic of Korea
    • Abstract:
      Background: Few studies in epidemiology have evaluated the effects of gene-environment interaction on oxidative stress, even though this interaction is an important etiologic factor in lung carcinogenesis. We investigated the effects of the genetic polymorphisms of paraoxonase 1 (PON1), smoking, and the interaction between the two on lung cancer risk and oxidative stress.
      Methods: This study's subjects consisted of 416 newly diagnosed lung cancer patients and an equal number of matched controls. The GoldenGate assay was used for genotypic analyses of the PON1 gene. Urinary 8-hydroxydeoxyguanosine (8-OHdG) and thiobarbituric acid reactive substances levels were measured as indicators of oxidative stress.
      Results: The PON1 rs662 AA genotype showed a significantly lower risk of lung cancer than the GG genotype (OR = 0.60, 95% CI: 0.36-0.99). The protective effect of the PON1 rs662 AA genotype on lung cancer risk was limited to non-smokers. Lung cancer patients who had the rs662 A allele showed a dose-dependent association between smoking status and oxidative stress markers. Among non-smoking lung cancer patients, urinary 8-OHdG levels were significantly lower in individuals with the rs662 GA and AA genotypes than in those with the GG genotype. Furthermore, we found a significant interaction effect between PON1 rs662 and smoking status on urinary 8-OHdG levels in lung cancer patients.
      Conclusions: Our results suggest that the protective effect of PON1 rs662 SNP against lung carcinogenesis and the induction of oxidative stress might be modulated by the interaction between PON1 genetic polymorphisms and tobacco smoking.
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    • Accession Number:
      EC 3.1.8.1 (Aryldialkylphosphatase)
      EC 3.1.8.1 (PON1 protein, human)
    • Publication Date:
      Date Created: 20150306 Date Completed: 20160128 Latest Revision: 20181113
    • Publication Date:
      20231215
    • Accession Number:
      PMC4350985
    • Accession Number:
      10.1371/journal.pone.0119100
    • Accession Number:
      25741997