title: Smoking and COX-2 functional polymorphisms interact to increase the risk of gastric cardia adenocarcinoma in Chinese population.
abstract: BACKGROUND
  Over-expression and increased activity of cyclooxygenase (COX)-2 induced by smoking has been implicated in the development of cancer. This study aimed to explore the interaction between smoking and functional polymorphisms of COX-2 in modulation of gastric cardia adenocarcinoma (GCA) risk.
  
  
  RESULTS
  Three COX-2 polymorphisms, including -1195G>A (rs689466), -765G>C (rs20417), and 587Gly>Arg (rs3218625), were genotyped in 357 GCA patients and 985 controls. In the multivariate logistic regression analysis, we found that the -1195AA, -765GC, and 587Arg/Arg genotypes were associated with increased risk of GCA (OR = 1.50, 95% CI = 1.05-2.13; OR = 2.06, 95% CI = 1.29-3.29 and OR = 1.67, 95% CI = 1.04-2.66, respectively). Haplotype association analysis showed that compared with G(-1195)-G(-765)- G(Gly587Arg), the A(-1195)-C(-765)-A(Gly587Arg) conferred an increased risk of GCA (OR = 2.49, 95% CI = 1.54-4.01). Moreover, significant multiplicative interactions were observed between smoking and these three polymorphisms of -1195G>A, -765G>C, and 587Gly>Arg, even after correction by false discovery rate (FDR) method for multiple comparisons (FDR-P(interaction) = 0.006, 5.239×10(-4) and 0.017, respectively). Similarly, haplotypes incorporating these three polymorphisms also showed significant interaction with smoking in the development of GCA (P for multiplicative interaction = 2.65×10(-6)).
  
  
  CONCLUSIONS
  These findings indicated that the functional polymorphisms of COX-2, in interaction with smoking, may play a substantial role in the development of GCA.
authors.affiliation: Department of Molecular Biology, College of Life Sciences, Hebei United University, Tangshan, China. jyxuemei@gmail.com
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Zhang
authors.forename: Rong
authors.initials: R
authors.lastname: Zhong
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Ju-Xiang
authors.initials: JX
authors.lastname: Yuan
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Chuang
authors.initials: C
authors.lastname: Sun
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhang
authors.forename: Wen-Guang
authors.initials: WG
authors.lastname: Song
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Miao
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology* / Q000235:genetics*; D000368:Aged; D044466:Asian People / Q000235:genetics; D002299:Cardia / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D013274:Stomach Neoplasms / Q000209:etiology* / Q000235:genetics*
chemical_list: D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human