An association between glutathione S-transferase P1 gene polymorphism and younger age at onset of lung carcinoma.
BACKGROUND
Among the genes that encode the glutathione S-transferase (GST) superfamily of Phase 2 metabolizing enzymes, GSTP1 has the highest expression in the lung. The polymorphic GSTP1 gene encodes glutathione S-transferase pi, which is an enzyme that detoxifies cigarette carcinogens, such as benzo-[a]-pyrene. The variant GSTP1 GG genotype is associated with lower enzymatic activity and higher DNA adduct levels in human lymphocytes compared with the AA genotype.


METHODS
The authors evaluated the association of GSTP1 genotypes with lung cancer in 1921 cases and 1343 controls of Caucasian descent by using polymerase chain reaction-restriction fragment length polymorphism techniques. The results were analyzed with multiple logistic regression adjusting for age, gender, smoking status, and pack-years. To investigate specifically the subset of younger lung cancer patients and controls, the effect of age (either as a dichotomous or continuous variable in separate models) was analyzed as a modifying factor of the association between the GSTP1 polymorphism and lung cancer.


RESULTS
The GSTP1 GG genotype was not associated with an overall increased risk of lung cancer (adjusted odds ratio, 1.02; 95% confidence interval [95% CI], 0.78-1.34) compared with the GSTP1 AA genotype. In both models that evaluated the gene-age interaction, an overall statistically significant interaction (P < .01) was observed between age and the GG genotype. However, for the model that included age as a dichotomous variable, the odds ratio of lung cancer risk with the GG genotype compared with the AA among individuals age </=50 years was 2.67 (95% CI, 1.36-5.22); in older individuals, the risk was 0.87 (95% CI, 0.65-1.2).


CONCLUSIONS
The GSTP1 GG genotype was associated with increased lung cancer susceptibility among younger study participants.
Miller
David P
DP
Department of Environmental Heath, Occupational Health Program, Harvard School of Public Health, Boston, Massachusetts, USA.
Asomaning
Kofi
K
Liu
Geoffrey
G
Wain
John C
JC
Lynch
Thomas J
TJ
Neuberg
Donna
D
Su
Li
L
Christiani
David C
DC
D000328:Adult; D017668:Age of Onset; D002277:Carcinoma / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
D051549:Glutathione S-Transferase pi