Open Access Research article

Polymorphism in COX-2 modifies the inverse association between Helicobacter pylori seropositivity and esophageal squamous cell carcinoma risk in Taiwan: a case control study

Huang-Ming Hu1, Chao-Hung Kuo123, Chien-Hung Lee45, I-Chen Wu2, Ka-Wo Lee67, Jang-Ming Lee8, Yih-Gang Goan9, Shah-Hwa Chou10, Ein-Long Kao10, Ming-Tsang Wu114 and Deng-Chyang Wu234*

Author Affiliations

1 Division of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan

2 Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

3 Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan

4 Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

5 Department of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan

6 Department of Otolaryngology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

7 Department of Otolaryngology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan

8 Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan

9 Department of Chest Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

10 Department of Chest Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

11 Department of Family Medicine, Graduate Institute of Occupational Safety and Health, Kaohsiung Medical University, Kaohsiung, Taiwan

For all author emails, please log on.

BMC Gastroenterology 2009, 9:37  doi:10.1186/1471-230X-9-37

Published: 23 May 2009

Abstract

Background

Overexpression of Cyclooxygenase-2 (COX-2) was observed in many types of cancers, including esophageal squamous cell carcinoma (ESCC). One functional SNP, COX-2 -1195G/A, has been reported to mediate susceptibility of ESCC in Chinese populations. In our previous study, the presence of Helicobacter pylori (H. pylori) was found to play a protective role in development of ESCC. The interaction of COX-2 and H. pylori in gastric cancer was well investigated. However, literature on their interaction in ESCC risk is scarce. The purpose of this study was to evaluate the association and interaction between COX-2 single nucleotide polymorphism (SNP), H. pylori infection and the risk of developing ESCC.

Methods

One hundred and eighty patients with ESCC and 194 controls were enrolled in this study. Personal data regarding related risk factors, including alcohol consumption, smoking habits and betel quid chewing, were collected via questionnaire. Genotypes of the COX-2 -1195 polymorphism were determined by PCR-based restriction fragment length polymorphism. H. pylori seropositivity was defined by immunochromatographic screening test. Data was analyzed by chi-squared tests and polytomous logistics regression.

Results

In analysis adjusting for the covariates and confounders, H. pylori seropositivity was found to be inversely association with the ESCC development (adjusted OR: 0.5, 95% CI: 0.3 – 0.9). COX-2 -1195 AA homozygous was associated with an increased risk of contracting ESCC in comparison with the non-AA group, especially among patients with H. pylori seronegative (adjusted OR ratio: 2.9, 95% CI: 1.2 – 7.3). The effect was strengthened among patients with lower third ESCC (adjusted OR ratio: 6.9, 95% CI 2.1 – 22.5). Besides, H. pylori seropositivity conveyed a notably inverse effect among patients with COX-2 AA polymorphism (AOR ratio: 0.3, 95% CI: 0.1 – 0.9), and the effect was observed to be enhanced for the lower third ESCC patients (AOR ratio: 0.09, 95% CI: 0.02 – 0.47, p for multiplicative interaction 0.008)

Conclusion

H. pylori seropositivity is inversely associated with the risk of ESCC in Taiwan, and COX-2 -1195 polymorphism plays a role in modifying the influence between H. pylori and ESCC, especially in lower third esophagus.