國家衛生研究院 NHRI:Item 3990099045/4387

NHRI > National Institute of Environmental Health Sciences > Ying-Chin Ko(2003-2009) > Periodical Articles > Item 3990099045/4387

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/4387

Title:	Up-regulation of inflammatory signalings by areca nut extract and role of Cyclooxygenase-2-1195G A polymorphism reveal risk of oral cancer
Authors:	Chiang, S;Chen, P;Lee, C;Ko, A;Lee, K;Lin, Y;Ho, P;Tu, H;Wu, D;Shieh, T;Ko, Y
Contributors:	Division of Environmental Health and Occupational Medicine
Abstract:	Because the mRNA expression of cyclooxygenase-2 (COX-2) is up-regulated by arecoline in human gingival fibroblasts, as shown in our previous study, we further investigated the mRNA expression level of COX-2 and its upstream effectors in three oral epithelial carcinoma cell lines (KB, SAS, and Ca9-22) by using areca nut extract (ANE) and saliva-reacted ANE (sANE). A case-control study of 377 oral squamous cell carcinoma (OSCC) patients and 442 controls was conducted to evaluate the gene-environment interaction between COX-2 promoter polymorphisms and substance use of alcohol, betel quid, and cigarettes (ABC) in risk of OSCC. The heterogeneous characteristics of the oral site and the COX-2 -1195G>A polymorphism in these cell lines showed diverse inflammatory response (KB?Ca9-22>SAS) after 24-hour ANE/sANE treatments, and the COX-2 up-regulation might be mostly elicited from alternative nuclear factor-κB activation. In the case-control study, betel chewing [adjusted odds ratios (aOR), 42.2] posed a much higher risk of OSCC than alcohol drinking and cigarette smoking (aORs, 2.4 and 1.8, respectively), whereas the COX-2 -1195A/A homozygote presented a potential genetic risk (OR, 1.55). The strongest joint effect for OSCC was seen in betel chewers with -1195A/A homozygote (aOR, 79.44). In the non-betel chewing group, the -1195A/G and A/A genotypes together with the combined use of alcohol and cigarettes increased risk to 15.1-fold and 32.1-fold, respectively, compared with the G/G genotype without substance use. Taken together, these findings illustrate a valuable insight into the potential role of the COX-2 promoter region in contributing to the development of betel-related OSCC, including ANE/sANE-induced transcriptional effects and enhanced joint effects of COX-2 -1195A allele with substance use of ABC.
Date:	2008-10-15
Relation:	Cancer Research. 2008 Oct 15;68(20):8489-8498.
Link to:	http://dx.doi.org/10.1158/0008-5472.can-08-0823
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0008-5472&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000260323400035
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=54349124402
Appears in Collections:	[Ying-Chin Ko(2003-2009)] Periodical Articles

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