Interaction of Cyclooxygenase-2 promoter polymorphisms with Helicobacter pylori infection and risk of gastric cancer

Authors

  • Xuemei Zhang,

    1. Department of Molecular biology, College of Life Sciences, Hebei United University, Tangshan, China
    2. Devision of Medical Genetics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas
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  • Rong Zhong,

    1. Department of Epidemiology and Biostatistics, and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Zhi Zhang,

    1. Department of Cancer Chemotherapy and Radiology, Tangshan Gongren Hospital, Tangshan, China
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  • Juxiang Yuan,

    1. Department of Epidemiology, College of Public Health, Tangshan United University, China
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  • Li Liu,

    1. Department of Epidemiology and Biostatistics, and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Yan Wang,

    1. Department of Epidemiology and Biostatistics, and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Susan Kadlubar,

    1. Devision of Medical Genetics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas
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  • Fumin Feng,

    1. Department of Epidemiology, College of Public Health, Tangshan United University, China
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  • Xiaoping Miao

    Corresponding author
    1. Department of Epidemiology and Biostatistics, and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    • Department of Epidemiology and Biostatistics, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
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  • X. Zhang and R. Zhong contributed equally to this work.

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. © 2011 Wiley Periodicals, Inc.

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