Abstract
Abstract The myeloperoxidase (MPO) −463G→A genetic polymorphism is associated with a reduced risk for lung cancer, but the underlying mechanism is not yet elucidated. Therefore, the impact of this polymorphism on MPO activity and lipophilic DNA adducts was studied in respectively bronchoalveolar lavage (BAL) fluid and cells, from 106 smoking Caucasian lung patients. MPO activity was determined spectrophotometrically, aromatic DNA adducts by 32P-postlabeling and MPO genotypes by RFLP analysis. Frequencies of MPO −463AA (13%), MPO −463AG (36%), and MPO −463GG (51%) were in line with earlier observations. MPO activity/neutrophil was lower in MPO −463AA (median 0.04 pU/cell) than in MPO −463AG (median 0.07 pU/cell) and MPO −463GG (median 0.14 pU/cell; P = 0.059) individuals. DNA adducts in BAL cells were measured in 11 MPO −463AA subjects and equal numbers of MPO −463AG and MPO −463GG subjects matched for smoking, age, gender, and clinical diagnosis. DNA adduct levels in MPO −463AA individuals (median 0.62 adducts/108 nucleotides) were lower than in MPO −463AG (median 1.51 adducts/108 nucleotides) and MPO −463GG (median 3.26 adducts/108 nucleotides; P = 0.003) subjects. Overall, no significant correlation was observed between amount of inhaled tar/day and DNA adduct levels. However, correlations improved considerably on grouping according to the MPO genotype; MPO −463AA subjects were the least responsive (R2 = 0.73, slope = 0.4, P = 0.01) followed by MPO −463AG subjects (R2 = 0.70, slope = 1.3, P = 0.01) and MPO −463GG patients (R2 = 0.67, slope = 2.8, P = 0.02). These data demonstrate that MPO −463AA/AG genotypes are associated with (a) reduced MPO activity in BAL fluid and (b) reduced smoking-related DNA adduct levels in BAL cells in a gene-dose manner. These data provide a plausible biological explanation for the reduced risk for lung cancer as observed in MPO −463AA/AG compared with MPO −463GG subjects.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
