RT Journal Article
SR Electronic
T1 Late-breaking abstract: Glutathione-S-transferase P1 Ile105Val polymorphism associated with elevated lung function and reduced risk of lung cancer and death in 66,000 individuals
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 2926
VO 44
IS Suppl 58
A1 Morten Dahl
A1 Marianne Nørskov
A1 Børge Nordestgaard
A1 Anne Tybjærg-Hansen
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/2926.abstract
AB Background: The enzyme glutathione-S-transferase (GST) P1 metabolises carcinogens from tobacco smoke in the lung. We tested whether genetically altered GSTP1 activity affects lung function and risk of lung cancer, tobacco-related cancer and death in the general population.Methods: We genotyped 66,069 individuals from the Danish general population for two functional polymorphisms in the GSTP1 gene (Ile105Val and Ala114Val), and recorded lung function, lung cancer, tobacco-related cancer, and death as outcomes.Results: Lung function was stepwise increased with Ile105Val genotype overall (P<0.01) and in smokers separately (P<0.01). Adjusted hazard ratios for lung cancer, tobacco-related cancer, and death were stepwise reduced with Ile105Val genotype (P≤0.02): homozygotes and heterozygotes had hazard ratios for lung cancer of 0.65 (0.47-0.90) and 0.94 (0.79-1.13), for tobacco-related cancer of 0.75 (0.60-0.92) and 0.93 (0.82-1.06), and for death of 0.87 (0.80-0.95) and 0.94 (0.89-0.99), respectively, as compared with Ile105Val non-carriers. The Ala114Val genotype associated with reduced mortality (P = 0.01), but not with lung function, lung cancer or tobacco-related cancer.Conclusion: The common GSTP1 Ile105Val variant was associated with elevated lung function and reduced risk of lung cancer, tobacco-related cancer, and death in the general population. The data support a role for GSTP1 in oxidant-mediated events influencing lung function, lung cancer, tobacco-related cancer and death, especially among smokers.