Genetic Variation in GSTP1, Lung Function, Risk of Lung Cancer, and Mortality
JOURNAL OF THORACIC ONCOLOGY
Authors: Norskov, Marianne S.; Dahl, Morten; Tybjaerg-Hansen, Anne
Abstract
Introduction: Glutathione S-transferase pi 1 metabolizes carcinogens from tobacco smoke in the lung. We tested whether genetically altered glutathione S-transferase pi 1 activity affects lung function and risk for tobacco-related cancer and mortality in the general population. Methods: We genotyped 66,069 individuals from the white general population for two common functional variants in the glutathione S-transferase pi 1 gene (GSTP1)-amino acid isoleucine 105 changed to a valine (Ile105Val) and amino acid alanine 114 changed to a valine (Ala114Val)- and recorded lung function, lung cancer, tobacco-related cancer, and death as outcomes. Results: Lung function was increased stepwise with the Ile105Val genotype overall (p < 0.01) and among smokers separately (p < 0.01). Adjusted hazard ratios for lung cancer, tobacco-related cancer, and death were reduced stepwise with the Ile105Val genotype (p < 0.02): Ile105Val homozygotes and heterozygotes versus noncarriers had hazard ratios for lung cancer of 0.64 (0.47-0.89) and 0.93 (0.78-1.11), for tobacco-related cancer of 0.74 (0.60-0.92) and 0.92 (0.81-1.04), and hazard ratios for death of 0.87 (0.80-0.95) and 0.94 (0.89-0.99), respectively. Population prevented fractions of lung cancer, tobacco-related cancer, and death due to Ile105Val homozygosity were 4%, 3% and 2%, respectively. The Ala114Val genotype was associated with reduced mortality (p < 0.01) but not with lung function, lung cancer, or tobacco-related cancer. Conclusion: GSTP1 Ile105Val was associated with increased lung function, reduced risk for lung cancer and tobacco-related cancer, and reduced all-cause mortality in the general population. (C) 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
Association of Genetic Ancestry With DNA Methylation Changes in Prostate Cancer Disparity
ANTICANCER RESEARCH
Authors: Apprey, Victor; Wang, Songping; Tang, Wei; Kittles, Rick A.; Southerland, William M.; Ittmann, Michael; Kwabi-Addo, Bernard
Abstract
Background: We hypothesized that ancestry-mediated methylated DNA changes may drive racial and ethnic disparity in prostate cancer (PCa). To test this hypothesis, we analyzed genetic ancestry and association with DNA methylation changes in PCa disparity. Materials and Methods: Pyrosequencing and ancestry informative markers were used for DNA methylation and genetic ancestry testing, respectively. Results: Using Spearman rho rank correlation test, the data demonstrated significant (p<0.05) and variable association between African-American ancestry and DNA methylation for all genes investigated in prostate tissues. Conclusion: Genetic ancestry influences DNA methylation and this modifying factor must be considered in epigenetic association studies in populations of admixed patients.