Glutathione peroxidase codon 198 polymorphism variant increases lung cancer risk.
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 alpha-Tocopherol, beta-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.
Ratnasinghe
D
D
Division of Clinical Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892-7058, USA. DR132K@NIH.gov
Tangrea
J A
JA
Andersen
M R
MR
Barrett
M J
MJ
Virtamo
J
J
Taylor
P R
PR
Albanes
D
D
D000367:Age Factors; D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism; D016022:Case-Control Studies; D003062:Codon; D005838:Genotype; D018095:Germ-Line Mutation; D005979:Glutathione Peroxidase / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking / Q000235:genetics; D014810:Vitamin E / Q000008:administration & dosage / Q000097:blood; D019207:beta Carotene / Q000008:administration & dosage / Q000097:blood; D000094765:Glutathione Peroxidase GPX1
D000975:Antioxidants; D003062:Codon; D019207:beta Carotene; D014810:Vitamin E; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human