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GSTM1, GSTT1, and GSTP1 polymorphism and lung cancer risk in relation to tobacco smoking.
Cancer Lett 2004; 208(1):65-74CL

Abstract

The impact of genetic polymorphisms in GSTM1, GSTP1 or GSTT1 on susceptibility to lung cancer has received particular interest since these enzymes play a central role in detoxification of major classes of tobacco carcinogens. In the current German study we investigated the role of GSTM1, GSTT1 and GSTP1 polymorphisms as a genetic modifier of risk for individuals with lung cancer as susceptible genotypes especially in relation to tobacco smoking. The GSTM1, the GSTP1 as well as GSTT1-polymorphism were determined by real time PCR analysis in 446 lung cancer patients and 622 controls. The observed allele frequencies of the GSTP1 polymorphism in the population were within the range described for Caucasians. Multivariate analyses of lung cancer patients, who carried at least one mutant variant allele of GSTP1 (OR=1.03; 95%-CI: 0.76-1.39) did not show any elevated risks. GSTM1 or GSTT1 null-genotypes were found in 47.3% resp. 18.5% of the controls and in 52.5% resp. 16.8% of the cancer patients. The estimated risk of the GSTM1 null genotype for lung cancer was OR=1.34 (95%-CI: 0.99-1.81) and for the GSTT1 null genotype OR=0.88 (95%-CI: 0.59-1.32). When analyzed by histology no individual subtype of lung cancer was strongly associated with the polymorphisms. Lung cancer risk rose significantly with higher cumulative cigarette consumption confirming the association with smoking-related lung cancer risk. Stratified analysis between tobacco smoking and variant genotypes revealed for heavy smokers (>60 pack-years) increasing risks at the presence for at least one copy of the GSTP1 variant allele OR=50.56 (95%-CI: 15.52-164.79). The corresponding risks for GSTM1 null genotypes were OR=112.08 (95%-CI: 23.02-545.71) and for the GSTT1 null-genotype OR=158.49 (95%-CI: 17.75-1415.06) in smokers >60 pack-years. Analysing the interaction between tobacco smoking and the genotypes, combined smoking and having the susceptible genotypes did not show a joint effect. In this study polymorphisms of the GSTM1, GSTT1 or GSTP1 had no relevant modifying effect on lung cancer risk and cumulative smoking dose.

Authors+Show Affiliations

Priv. Doz. Dr. med. Joachim Schneider, Institut und Poliklinik für Arbeits-und Sozialmedizin, der Justus-Liebig Universität, Aulweg 129/III, D-35385 Giessen, Germany. joachim.schneider@arbmed.med.uni-giessen.de

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15105047

Citation

Schneider, Joachim, et al. "GSTM1, GSTT1, and GSTP1 Polymorphism and Lung Cancer Risk in Relation to Tobacco Smoking." Cancer Letters, vol. 208, no. 1, 2004, pp. 65-74.
Schneider J, Bernges U, Philipp M, et al. GSTM1, GSTT1, and GSTP1 polymorphism and lung cancer risk in relation to tobacco smoking. Cancer Lett. 2004;208(1):65-74.
Schneider, J., Bernges, U., Philipp, M., & Woitowitz, H. J. (2004). GSTM1, GSTT1, and GSTP1 polymorphism and lung cancer risk in relation to tobacco smoking. Cancer Letters, 208(1), pp. 65-74.
Schneider J, et al. GSTM1, GSTT1, and GSTP1 Polymorphism and Lung Cancer Risk in Relation to Tobacco Smoking. Cancer Lett. 2004 May 10;208(1):65-74. PubMed PMID: 15105047.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - GSTM1, GSTT1, and GSTP1 polymorphism and lung cancer risk in relation to tobacco smoking. AU - Schneider,Joachim, AU - Bernges,Ulrike, AU - Philipp,Monika, AU - Woitowitz,Hans-Joachim, PY - 2003/09/21/received PY - 2004/01/05/revised PY - 2004/01/07/accepted PY - 2004/4/24/pubmed PY - 2004/6/29/medline PY - 2004/4/24/entrez SP - 65 EP - 74 JF - Cancer letters JO - Cancer Lett. VL - 208 IS - 1 N2 - The impact of genetic polymorphisms in GSTM1, GSTP1 or GSTT1 on susceptibility to lung cancer has received particular interest since these enzymes play a central role in detoxification of major classes of tobacco carcinogens. In the current German study we investigated the role of GSTM1, GSTT1 and GSTP1 polymorphisms as a genetic modifier of risk for individuals with lung cancer as susceptible genotypes especially in relation to tobacco smoking. The GSTM1, the GSTP1 as well as GSTT1-polymorphism were determined by real time PCR analysis in 446 lung cancer patients and 622 controls. The observed allele frequencies of the GSTP1 polymorphism in the population were within the range described for Caucasians. Multivariate analyses of lung cancer patients, who carried at least one mutant variant allele of GSTP1 (OR=1.03; 95%-CI: 0.76-1.39) did not show any elevated risks. GSTM1 or GSTT1 null-genotypes were found in 47.3% resp. 18.5% of the controls and in 52.5% resp. 16.8% of the cancer patients. The estimated risk of the GSTM1 null genotype for lung cancer was OR=1.34 (95%-CI: 0.99-1.81) and for the GSTT1 null genotype OR=0.88 (95%-CI: 0.59-1.32). When analyzed by histology no individual subtype of lung cancer was strongly associated with the polymorphisms. Lung cancer risk rose significantly with higher cumulative cigarette consumption confirming the association with smoking-related lung cancer risk. Stratified analysis between tobacco smoking and variant genotypes revealed for heavy smokers (>60 pack-years) increasing risks at the presence for at least one copy of the GSTP1 variant allele OR=50.56 (95%-CI: 15.52-164.79). The corresponding risks for GSTM1 null genotypes were OR=112.08 (95%-CI: 23.02-545.71) and for the GSTT1 null-genotype OR=158.49 (95%-CI: 17.75-1415.06) in smokers >60 pack-years. Analysing the interaction between tobacco smoking and the genotypes, combined smoking and having the susceptible genotypes did not show a joint effect. In this study polymorphisms of the GSTM1, GSTT1 or GSTP1 had no relevant modifying effect on lung cancer risk and cumulative smoking dose. SN - 0304-3835 UR - https://www.unboundmedicine.com/medline/citation/15105047/GSTM1_GSTT1_and_GSTP1_polymorphism_and_lung_cancer_risk_in_relation_to_tobacco_smoking_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304383504000412 DB - PRIME DP - Unbound Medicine ER -