Cytochrome P4502E1 (CYP2E1) genetic polymorphism in a case-control study of gastric cancer and liver disease.
Cytochrome P4502E1 (CYP2E1) activates carcinogenic N-nitrosamines, benzene, urethane and other low molecular weight compounds. This enzyme is also inducible by ethanol, and metabolizes alcohol. A restriction fragment length polymorphism (RFLP) using the Rsa I restriction enzyme has been identified in the CYP2E1 transcription regulatory region; recent studies suggest that this polymorphism may affect gene expression. We investigated the frequency of the Rsa I RFLP in a Japanese population in relation to gastric cancer and liver disease susceptibility. The frequency of this polymorphism was determined in 150 gastric cancer, 16 hepatocellular cancer, 48 liver cirrhosis and 203 benign gastric disease (controls) patients. This preliminary study shows no association of the specific genotype with gastric cancer in all subjects (odds ratio = 1.04, 95% CI = 0.74-3.08 for the heterozygote and 0.57, 95% CI = 0.22-1.50 for the homozygous rare allele, respectively). To further confirm this lack of association, an age and gender matched case-control study should be performed. Separately, there was no association of the Rsa I RFLP with hepatocellular carcinoma (p = 0.911), but there was a suggested difference between the non-viral associated liver cirrhosis patients and control patients. Thus, this polymorphism may be related to ethanol metabolism and consequential liver diseases in a Japanese population.
Kato
S
S
First Department of Surgery, Nippon Medical School, Tokyo, Japan.
Onda
M
M
Matsukura
N
N
Tokunaga
A
A
Tajiri
T
T
Kim
D Y
DY
Tsuruta
H
H
Matsuda
N
N
Yamashita
K
K
Shields
P G
PG
D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics*; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006580:Genetic Carrier Screening; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008103:Liver Cirrhosis / Q000201:enzymology / Q000235:genetics*; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D016017:Odds Ratio; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012016:Reference Values; D012045:Regulatory Sequences, Nucleic Acid; D012727:Sex Characteristics; D013272:Stomach Diseases / Q000201:enzymology / Q000235:genetics; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics*; D014158:Transcription, Genetic
D017931:DNA Primers; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating