title: Interaction of cyclooxygenase-2 promoter polymorphisms with Helicobacter pylori infection and risk of gastric cancer.
abstract: Overexpression of cyclooxygenase (COX)-2 has been implicated in the development of cancer. This study aimed to evaluate the relationship between genetic variants in COX-2 promoter interacting with Helicobacter pylori and the susceptibility to gastric cancer (GC). Three COX-2 polymorphisms -1290A>G (rs689465), -1195G>A (rs689466), and -765G>C (rs20417) were genotyped in 323 GC patients and 944 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression model. In GC patients, the ORs were 2.33 (95% CI = 1.50-3.63) and 2.70 (95% CI = 1.68-4.33) for -1195AA and -765CG genotype carriers, respectively. Haplotype analysis showed all -1195A allele-containing haplotypes, except G(-1290)-A(-1195)-G(-765), were associated with increased risk for GC, compared with the A(-1290)-G(-1195)-G(-765) haplotype. Moreover, significant multiplicative and additive interactions were observed between H. pylori infection and all these three polymorphisms, and H. pylori-infected subjects carrying the variant allele of -1290A>G, -1195G>A, or -765G>C had increased risk of GC compared with non-H. pylori-infected subjects with wild-type allele (OR = 4.10, 95% CI = 1.90-8.83; OR = 3.46, 95% CI = 1.31-9.11; and OR = 3.32, 95% = 1.27-8.73, respectively). Our results suggested that the COX-2 promoter polymorphisms were associated with increased risk of GC, especially interacting with H. pylori infection.
authors.affiliation: Department of Molecular biology, College of Life Sciences, Hebei United University, Tangshan, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.forename: Rong
authors.initials: R
authors.lastname: Zhong
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhang
authors.forename: Juxiang
authors.initials: J
authors.lastname: Yuan
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Susan
authors.initials: S
authors.lastname: Kadlubar
authors.forename: Fumin
authors.initials: F
authors.lastname: Feng
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Miao
mesh_terms: D000368:Aged; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006239:Haplotypes; D016481:Helicobacter Infections / Q000150:complications*; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000209:etiology* / Q000235:genetics*
chemical_list: D051546:Cyclooxygenase 2