Myeloperoxidase G-463A polymorphism and lung cancer: a HuGE genetic susceptibility to environmental carcinogens pooled analysis.
Myeloperoxidase is a phase I metabolic enzyme that converts the metabolites of benzo[a]pyrene from tobacco smoke into highly reactive epoxides. A polymorphism in the promoter region of myeloperoxidase (463G-->A) has been found to be inversely associated with lung cancer; differences in the association with age and gender have been suggested. We conducted a pooled analysis of individual data from 10 studies (3688 cases and 3874 controls) from the Genetic Susceptibility to Environmental Carcinogens database. The odds ratio for lung cancer was 0.88 (95% confidence interval: 0.80-0.97) for the AG variant of myeloperoxidase G-463A polymorphism, and 0.71 (95% confidence interval: 0.57-0.88) for the AA variant after adjusting for smoking, age, gender, and ethnicity. The inverse association between lung cancer and myeloperoxidase G-463A polymorphism was equally found in males and females (odds ratio for the AA genotype 0.73 [95% confidence interval: 0.56-0.96] and 0.67 [95% confidence interval: 0.46-0.98], respectively), without differences in the association according to age in the two genders. The myeloperoxidase G-463A polymorphism was significantly protective in "ever" smokers but not in "never" smokers. Myeloperoxidase is a key enzyme in tobacco-induced carcinogenesis.
Taioli
Emanuela
E
University of Pittsburgh, Cancer Institute, Pittsburgh, Pensylvania 15232, USA.
Benhamou
Simone
S
Bouchardy
Christine
C
Cascorbi
Ingolf
I
Cajas-Salazar
Nohelia
N
Dally
Heike
H
Fong
Kwun M
KM
Larsen
Jill E
JE
Le Marchand
Loic
L
London
Stephanie J
SJ
Risch
Angela
A
Spitz
Margaret R
MR
Stucker
Isabelle
I
Weinshenker
Brian
B
Wu
Xifeng
X
Yang
Ping
P
D000367:Age Factors; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D016017:Odds Ratio; D009195:Peroxidase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects
D009195:Peroxidase