TY - JOUR
T1 - Polymorphisms in polycyclic aromatic hydrocarbon metabolism and conjugation genes, interactions with smoking and prostate cancer risk
AU - Nock, Nora L.
AU - Liu, Xin
AU - Cicek, Mine S.
AU - Li, Li
AU - Macarie, Flavius
AU - Rybicki, Benjamin A.
AU - Plummer, Sarah J.
AU - MacLennan, Gregory T.
AU - Casey, Graham
AU - Witte, John S.
PY - 2006/4
Y1 - 2006/4
N2 - The relationship between cigarette smoking and prostate cancer remains unclear. Any potential association may depend on the individuals' ability to metabolize and detoxify cigarette carcinogens - such as polycyclic aromatic hydrocarbons. To investigate this, we studied the association between prostate cancer and smoking, as well as the main and modifying effects of functional polymorphisms in genes that metabolize polycyclic aromatic hydrocarbons (CYP1A1 Ile462Val, microsomal epoxide hydrolase His139Arg) and detoxify reactive derivatives (GSTM1 null deletion, GSTT1 null deletion, GSTP1 Ile105Val and Ala114Val) using a family-based case-control design (439 prostate cancer cases and 479 brother controls). Within the entire study population, there were no main effects for smoking or any of the polymorphisms. However, the nondeleted GSTM1 allele was inversely associated with prostate cancer [odds ratio (OR), 0.50; 95% confidence interval (95% CI), 0.26-0.94] among men with less aggressive disease (Gleason score < 7 and clinical tumor stage < T2c) and positively associated (OR, 1.68; 95% CI, 1.01-2.79) with prostate cancer in men with more aggressive disease (Gleason score ≥ 7 or clinical tumor stage ≥ T2c). We also found a statistically significant negative multiplicative interaction between the GSTM1 nondeleted allele and heavy smoking (> 20 pack-years) in the total study population (P = 0.01) and in Caucasians (P = 0.01). Among Caucasians, heavy smoking increased prostate cancer risk nearly 2-fold in those with the GSTM1 null genotype (OR, 1.73; 95% CI, 0.99-3.05) but this increased risk was not observed in heavy smokers who carried the GSTM1 nondeleted allele (OR, 0.95; 95% CI, 0.53-1.71). Our results highlight the importance of considering genetic modifiers of carcinogens when evaluating smoking in prostate cancer.
AB - The relationship between cigarette smoking and prostate cancer remains unclear. Any potential association may depend on the individuals' ability to metabolize and detoxify cigarette carcinogens - such as polycyclic aromatic hydrocarbons. To investigate this, we studied the association between prostate cancer and smoking, as well as the main and modifying effects of functional polymorphisms in genes that metabolize polycyclic aromatic hydrocarbons (CYP1A1 Ile462Val, microsomal epoxide hydrolase His139Arg) and detoxify reactive derivatives (GSTM1 null deletion, GSTT1 null deletion, GSTP1 Ile105Val and Ala114Val) using a family-based case-control design (439 prostate cancer cases and 479 brother controls). Within the entire study population, there were no main effects for smoking or any of the polymorphisms. However, the nondeleted GSTM1 allele was inversely associated with prostate cancer [odds ratio (OR), 0.50; 95% confidence interval (95% CI), 0.26-0.94] among men with less aggressive disease (Gleason score < 7 and clinical tumor stage < T2c) and positively associated (OR, 1.68; 95% CI, 1.01-2.79) with prostate cancer in men with more aggressive disease (Gleason score ≥ 7 or clinical tumor stage ≥ T2c). We also found a statistically significant negative multiplicative interaction between the GSTM1 nondeleted allele and heavy smoking (> 20 pack-years) in the total study population (P = 0.01) and in Caucasians (P = 0.01). Among Caucasians, heavy smoking increased prostate cancer risk nearly 2-fold in those with the GSTM1 null genotype (OR, 1.73; 95% CI, 0.99-3.05) but this increased risk was not observed in heavy smokers who carried the GSTM1 nondeleted allele (OR, 0.95; 95% CI, 0.53-1.71). Our results highlight the importance of considering genetic modifiers of carcinogens when evaluating smoking in prostate cancer.
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U2 - 10.1158/1055-9965.EPI-05-0826
DO - 10.1158/1055-9965.EPI-05-0826
M3 - Article
C2 - 16614120
AN - SCOPUS:33646263609
SN - 1055-9965
VL - 15
SP - 756
EP - 761
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 4
ER -