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Division of Clinical Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892-7058 [D. R., J. A. T., P. R. T., D. A.]; New Chemical Entities, Inc., Thetagen Division, Bothell, Washington 98011 [M. R. A.]; Information Management Services, Inc., Silver Spring, Maryland 20904 [M. J. B.]; and National Public Health Institute, SF–00300 Helsinki, Finland [J. V.]
Human cellular glutathione peroxidase 1 (hGPX1) is a selenium-dependent
enzyme that participates in the detoxification of hydrogen peroxide and
a wide range of organic peroxides. We conducted a case-control study
nested within the 
-Tocopherol, ß-Carotene Cancer Prevention Study
cohort to evaluate the association between the proline to leucine
polymorphism at codon 198 of hGPX1 and lung cancer risk.
Cases (n = 315) were matched to controls
on age (±5 years), intervention group, and study clinic using
incidence density sampling in a 1:1 ratio. The prevalence of the hGPX1
Pro198leu variant allele was 58% for controls
and 71% for cases (P < 0.001). Using
conditional logistic regression, we found a significant association
between hGPX1 genotype and lung cancer risk. The odds ratio
for heterozygotes was 1.8 (95% confidence interval, 1.2–2.8) and 2.3
(95% confidence interval, 1.3–3.8) for homozygous variants compared
to wild-type individuals. Due to its high prevalence, the
hGPX1 variant may contribute significantly to lung cancer
risk among Caucasians but not among ethnic Chinese who do not exhibit
this polymorphism.
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