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


CONCLUSIONS
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.
Hu
Huang-Ming
HM
Division of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan. huhuangming@ms66.url.com.tw
Kuo
Chao-Hung
CH
Lee
Chien-Hung
CH
Wu
I-Chen
IC
Lee
Ka-Wo
KW
Lee
Jang-Ming
JM
Goan
Yih-Gang
YG
Chou
Shah-Hwa
SH
Kao
Ein-Long
EL
Wu
Ming-Tsang
MT
Wu
Deng-Chyang
DC
D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006306:Health Surveys; D016481:Helicobacter Infections / Q000150:complications*; D016480:Helicobacter pylori; D006720:Homozygote; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D013624:Taiwan
D051546:Cyclooxygenase 2