Cytochrome p450 2E1 polymorphisms and the risk of gastric cardia cancer.
OBJECTIVE
Genetic polymorphisms of drug-metabolizing enzymes have recently been shown to affect susceptibility to chemical carcinogenesis. Cytochrome P450 2E1 (CYP2E1) enzyme catalyzes the metabolism of many procarcinogens, such as N-nitrosamines and related compounds. The gene coding for this enzyme is polymorphic and thus may play a role in gastric cardia cancer (GCC) etiology. In this hospital-based case-control study, we evaluate the relationship between genetic polymorphisms of CYP2E1 and the risk of GCC.


METHODS
The study subjects comprised 159 histologically confirmed GCC cases identified via hospital cancer registry and surgical records at five hospitals in Fuzhou, Fujian Province, China, between April and November 2001. Controls were 192 patients admitted to the same hospitals for nonmalignant conditions. The genotypes of CYP2E1 were detected by a PCR-based RFLP assay. The odds ratios were estimated by logistic regression analyses and were adjusted for potential confounding factors.


RESULTS
The distribution of three genotypes of CYP2E1 in GCC cases and controls was significantly different (chi(2) = 16.04, P<0.01). The frequency of the CYP2E1 (c1/c1) genotype in GCC cases and controls was 60.4% and 40.1%, respectively. The CYP2E1 (c1/c1) genotype was associated with an increased risk for GCC (the adjusted (OR) was 2.37, 95% confidence interval (CI): 1.52-3.70). Subjects who carried the CYP2E1 (c1/c1) genotype and were habitual smokers were at a significantly higher risk of developing GCC (OR = 4.68, 95%CI: 2.19-10.04) compared with those who had the CYP2E1 (c1/c2 or c2/c2) genotype and did not smoke.


CONCLUSIONS
These results suggest that the CYP2E1 genotype may influence individual susceptibility to development of GCC, and that the risk increases significantly in smokers.
Cai
Lin
L
Department of Epidemiology, UCLA School of Public Health, 71-225 CHS, Box 951772, 10833 Le Conte Avenue, Los Angeles, CA 90095-1772, USA. lcaiin@ucla.edu
Zheng
Zong-Li
ZL
Zhang
Zuo-Feng
ZF
D000368:Aged; D002299:Cardia / Q000473:pathology; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D013274:Stomach Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology
D019392:Cytochrome P-450 CYP2E1