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Up-regulation of inflammatory signalings by areca nut extract and role of cyclooxygenase-2 -1195G>a polymorphism reveal risk of oral cancer.
Cancer Res. 2008 Oct 15; 68(20):8489-98.CR

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-kappaB 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.

Authors+Show Affiliations

Graduate Institute of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Chung-Ho Memorial Hospital, Kaohsiung, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18922923

Citation

Chiang, Shang-Lun, et al. "Up-regulation of Inflammatory Signalings By Areca Nut Extract and Role of Cyclooxygenase-2 -1195G>a Polymorphism Reveal Risk of Oral Cancer." Cancer Research, vol. 68, no. 20, 2008, pp. 8489-98.
Chiang SL, Chen PH, Lee CH, et al. Up-regulation of inflammatory signalings by areca nut extract and role of cyclooxygenase-2 -1195G>a polymorphism reveal risk of oral cancer. Cancer Res. 2008;68(20):8489-98.
Chiang, S. L., Chen, P. H., Lee, C. H., Ko, A. M., Lee, K. W., Lin, Y. C., Ho, P. S., Tu, H. P., Wu, D. C., Shieh, T. Y., & Ko, Y. C. (2008). Up-regulation of inflammatory signalings by areca nut extract and role of cyclooxygenase-2 -1195G>a polymorphism reveal risk of oral cancer. Cancer Research, 68(20), 8489-98. https://doi.org/10.1158/0008-5472.CAN-08-0823
Chiang SL, et al. Up-regulation of Inflammatory Signalings By Areca Nut Extract and Role of Cyclooxygenase-2 -1195G>a Polymorphism Reveal Risk of Oral Cancer. Cancer Res. 2008 Oct 15;68(20):8489-98. PubMed PMID: 18922923.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Up-regulation of inflammatory signalings by areca nut extract and role of cyclooxygenase-2 -1195G>a polymorphism reveal risk of oral cancer. AU - Chiang,Shang-Lun, AU - Chen,Ping-Ho, AU - Lee,Chien-Hung, AU - Ko,Albert Min-Shan, AU - Lee,Ka-Wo, AU - Lin,Ying-Chu, AU - Ho,Pei-Shan, AU - Tu,Hung-Pin, AU - Wu,Deng-Chyang, AU - Shieh,Tien-Yu, AU - Ko,Ying-Chin, PY - 2008/10/17/pubmed PY - 2008/11/8/medline PY - 2008/10/17/entrez SP - 8489 EP - 98 JF - Cancer research JO - Cancer Res VL - 68 IS - 20 N2 - 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-kappaB 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. SN - 1538-7445 UR - https://www.unboundmedicine.com/medline/citation/18922923/Up_regulation_of_inflammatory_signalings_by_areca_nut_extract_and_role_of_cyclooxygenase_2__1195G>a_polymorphism_reveal_risk_of_oral_cancer_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=18922923 DB - PRIME DP - Unbound Medicine ER -