TY - JOUR
T1 - Association between haplotypes of manganese superoxide dismutase (SOD2), smoking, and lung cancer risk
AU - Gallagher, Carla J.
AU - Ahn, Kwangmi
AU - Knipe, Ashley L.
AU - Dyer, Anne Marie
AU - Richie, John P.
AU - Lazarus, Philip
AU - Muscat, Joshua E.
N1 - Funding Information:
This study was supported by research grants (PO1 CA68384 and K07 CA104231) from the National Cancer Institute and (PA-DOH 4100038714) from the Pennsylvania Department of Health, and the Functional Genomics Core Facility at Penn State University College of Medicine.
PY - 2009/1/1
Y1 - 2009/1/1
N2 - Tobacco smoke contains high concentrations of reactive oxygen species (ROS) that can damage DNA, proteins, and lipids. Manganese superoxide dismutase (SOD2) catalyzes the dismutation of superoxide radicals into hydrogen peroxide and protects against oxidative stress in lung tissues. Three tagSNPs were identified in one block of high linkage disequilibrium that spans the entire SOD2 gene and 5-kb promoter region. These tagSNPs, representing four haplotypes (TAA, TCA, TCG, CCG), were genotyped in 372 lung cancer cases and 605 controls. There was no association between the haplotype frequencies and the overall lung cancer risk. The TCG haplotype (6% in controls) was significantly associated with a lower risk of lung cancer in light smokers (< median pack-years; P value = 0.02) but not in heavy smokers. In histologic-specific analysis, the TCG haplotype was significantly associated with a reduced risk of lung adenocarcinoma (odds ratio = 0.39, 95% CI 0.17-0.88), but an inverse association with squamous cell carcinoma was not significant. The association with adenocarcinoma was most apparent in light smokers (haplotype-specific P value = 0.005); none of the 61 case subjects with adenocarcinoma had the TCG allele. This study suggests that subjects with the SOD2 TCG haplotype may be at decreased risk for lung adenocarcinoma and that this association may depend on smoking amount.
AB - Tobacco smoke contains high concentrations of reactive oxygen species (ROS) that can damage DNA, proteins, and lipids. Manganese superoxide dismutase (SOD2) catalyzes the dismutation of superoxide radicals into hydrogen peroxide and protects against oxidative stress in lung tissues. Three tagSNPs were identified in one block of high linkage disequilibrium that spans the entire SOD2 gene and 5-kb promoter region. These tagSNPs, representing four haplotypes (TAA, TCA, TCG, CCG), were genotyped in 372 lung cancer cases and 605 controls. There was no association between the haplotype frequencies and the overall lung cancer risk. The TCG haplotype (6% in controls) was significantly associated with a lower risk of lung cancer in light smokers (< median pack-years; P value = 0.02) but not in heavy smokers. In histologic-specific analysis, the TCG haplotype was significantly associated with a reduced risk of lung adenocarcinoma (odds ratio = 0.39, 95% CI 0.17-0.88), but an inverse association with squamous cell carcinoma was not significant. The association with adenocarcinoma was most apparent in light smokers (haplotype-specific P value = 0.005); none of the 61 case subjects with adenocarcinoma had the TCG allele. This study suggests that subjects with the SOD2 TCG haplotype may be at decreased risk for lung adenocarcinoma and that this association may depend on smoking amount.
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U2 - 10.1016/j.freeradbiomed.2008.09.018
DO - 10.1016/j.freeradbiomed.2008.09.018
M3 - Article
C2 - 18930810
AN - SCOPUS:57449083224
SN - 0891-5849
VL - 46
SP - 20
EP - 24
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 1
ER -