CYP2A6 gene deletion reduces susceptibility to lung cancer.
CYP2A6 is an enzyme with a high ability to activate a nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), to its potent and ultimate carcinogen. In the present study, we investigated the relationship between genetic polymorphism of CYP2A6 and lung cancer risk in a case-control study of Japanese subjects. Genotyping of the CYP2A6 gene in both healthy volunteers and lung cancer patients was conducted. The frequency with which the subjects carried homozygotes of the CYP2A6 gene deletion-type mutation (deletion), which causes lack of the enzyme activity, was lower in the lung cancer patients than in the healthy control subjects. The odds ratio (OR) of the group homozygous for the deletion was significantly lower and calculated to be 0.25 (95% CI; 0.08-0.83) when the OR for the population with homozygotes of the CYP2A6 wild-type gene was defined as 1.00. In the allelic-base analysis, there was also a significant decrease in the OR for the deletion allele. These data suggest that deficient CYP2A6 activity due to genetic polymorphism reduces lung cancer risk.
Miyamoto
M
M
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, 060-0812, Japan.
Umetsu
Y
Y
Dosaka-Akita
H
H
Sawamura
Y
Y
Yokota
J
J
Kunitoh
H
H
Nemoto
N
N
Sato
K
K
Ariyoshi
N
N
Kamataki
T
T
D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases; D016022:Case-Control Studies; D065637:Cytochrome P-450 CYP2A6; D003577:Cytochrome P-450 Enzyme System / Q000172:deficiency / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000172:deficiency / Q000235:genetics*; D016017:Odds Ratio; D012307:Risk Factors
D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6