Cytochrome P4502E1 genetic polymorphisms and risk of nasopharyngeal carcinoma: results from a case-control study conducted in Taiwan.
CYP2E1 is responsible for the metabolic activation of nitrosamines believed to be involved in the pathogenesis of various tumors. Nasopharyngeal carcinoma (NPC) is a tumor thought to be linked to nitrosamine exposure. To investigate the possible role of CYP2E1 genetic polymorphisms in the etiology of this tumor, we investigated 50 histologically confirmed NPC cases from Taiwan and 50 controls matched to cases on age, sex, and residence. Samples were examined for RFLPs in the CYP2E1 gene by PCR amplification followed by digestion with DraI and RsaI. Among healthy controls, the allelic frequency of wild-type and variant forms of CYP2E1 were 79 and 21%, respectively, using DraI enzyme digestion and 82 and 18%, respectively, using RsaI enzyme digestion. As compared with individuals who were homozygous for the wild-type CYP2E1 gene, those found to be homozygous for the variant form of the gene by DraI digestion were at a 5-fold excess risk of disease (95% confidence interval = 0.95-16). Similarly, subjects homozygous for the variant form of the CYP2E1 gene by RsaI digestion were at 7.7-fold excess risk of developing NPC (95% confidence interval = 0.87-68). Individuals found to be heterozygous for the gene were at similar risk of disease compared to those homozygous for the wild-type gene. A strong association was observed between the RFLPs detected by DraI and RsaI digestion of CYP2E1; a correlation coefficient of 0.86 for controls and 0.91 for cases was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Hildesheim
A
A
Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, Maryland 20892-7374, USA.
Chen
C J
CJ
Caporaso
N E
NE
Cheng
Y J
YJ
Hoover
R N
RN
Hsu
M M
MM
Levine
P H
PH
Chen
I H
IH
Chen
J Y
JY
Yang
C S
CS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D016001:Confidence Intervals; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009303:Nasopharyngeal Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D009602:Nitrosamines / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology
D009602:Nitrosamines; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating