Interaction models of CYP1A1, GSTM1 polymorphisms and tobacco smoking in intestinal gastric cancer.
OBJECTIVE
To explore the interaction models of the cytochrome P-450 (CYP) 1A1 Val variant and glutathione S-transferase (GST) M1 null polymorphisms with tobacco smoking in the occurrence of intestinal gastric cancer.


METHODS
A community-based case-control study was conducted in Yangzhong. Subjects included 114 intestinal types of gastric cancer with endoscopic and pathological diagnosis during January 1997 and December 1998, and 693 controls selected from their spouse, siblings or siblings-in-law who had no history of digestive system cancer. Logistic regression was used to estimate the interaction models.


RESULTS
The frequency of the CYP1A1 Val variant allele in cases did not differ from that in controls. The OR of GSTM1 null genotype was 2.0 (95% confidence interval (95%CI): 1.2-3.1, P<0.01). It showed a significant type 2 form of interaction model when both CYP1A1 Val variant allele and former tobacco smoking existed (i.e., among the multiplicative effects, the disease risk is increased by the tobacco exposure alone but not by the CYP1A1 variant alone). The interaction index gamma was 2.8, and OR(eg) (95%CI) was 5.0 (1.9-13.4). GSTM1 null genotype and former tobacco smoking were significant in a type 4 interaction model (i.e., the disease risk is increased by GSTM1 null genotype or tobacco exposure alone among the multiplicative effects). The interaction index gamma and OR(eg) (95%CI) were 3.4 and 8.4 (3.4-20.9), respectively.


CONCLUSIONS
Different interaction models of CYP1A1 Val variant allele and GSTM1 null genotype with tobacco smoking will contribute to understanding carcinogenic mechanism, but there is a need to further investigate in larger scale studies.
Shen
Jing
J
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 701 West 168th Street (Room 505), New York, NY 10032, USA. js2182@columbia.edu
Wang
Run-Tian
RT
Xu
Yao-Chu
YC
Wang
Li-Wei
LW
Wang
Xin-Ru
XR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D003043:Cocarcinogenesis; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011110:Polymorphism, Genetic; D012907:Smoking / Q000009:adverse effects; D013274:Stomach Neoplasms / Q000201:enzymology / Q000209:etiology* / Q000235:genetics
D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase