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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. METHODS AND FINDINGS: 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)). CONCLUSION: These findings indicated that the functional polymorphisms of COX-2, in interaction with smoking, may play a substantial role in the development of GCA.

SUBMITTER: Zhang XM 

PROVIDER: S-EPMC3136492 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Smoking and COX-2 functional polymorphisms interact to increase the risk of gastric cardia adenocarcinoma in Chinese population.

Zhang Xue-Mei XM   Zhong Rong R   Liu Li L   Wang Ying Y   Yuan Ju-Xiang JX   Wang Peng P   Sun Chuang C   Zhang Zhi Z   Song Wen-Guang WG   Miao Xiao-Ping XP  

PloS one 20110714 7


<h4>Background</h4>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.<h4>Methods and findings</h4>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 t  ...[more]

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