Influence of a mutation reducing the catalytic activity of the cytochrome P450 CYP2D6 on lung cancer susceptibility.
The possible association between lung cancer and the CYP2D6*9 mutant allele, which reduces the catalytic activity of cytochrome P450 CYP2D6, was examined by PCR-SSCP using peripheral blood DNA from 249 cases of lung cancer and 265 controls, with detailed data on smoking. The CYP2D6*9 mutant allele was present in 4.9% of controls and 6% of cases. Adjusted for age, hospital and smoking, the odds ratio (OR) of lung cancer associated with the presence of the CYP2D6*9 mutant allele was 1.2 [95% confidence interval (CI) 0.5-2.9]. According to histological type, adenocarcinoma and small cell carcinoma were not associated with the presence of the CYP2D6*9 mutant allele and a non-significant higher occurrence of the mutant allele was observed for squamous cell carcinoma (OR 1.74, 95% CI 0.6-4.8). Moreover, no associations were observed upon stratification by number of pack-years of cigarette smoking. These results do not confirm an earlier report that this CYP2D6*9 mutant allele may be an additional risk factor for the development of lung cancer.
Legrand
M
M
Laboratoire de Biochimie et Biologie Moleculaire de l'Hopital Calmette, Centre Hospitalier Regional et Universitaire de Lille, France.
Stucker
I
I
Marez
D
D
Sabbagh
N
N
Lo-Guidice
J M
JM
Broly
F
F
D000483:Alleles; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics*; D018288:Carcinoma, Small Cell / Q000201:enzymology / Q000235:genetics*; D002384:Catalysis; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics*; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D013329:Structure-Activity Relationship
D019389:Cytochrome P-450 CYP2D6