Up-regulation of Inflammatory Signalings by Areca Nut Extract and Role ofCyclooxygenase-2−1195G>A Polymorphism Reveal Risk of Oral Cancer

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 geneenvironment 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 À1195G>A polymorphism in these cell lines showed diverse inflammatory response (KBJCa9-22>SAS) after 24-hour ANE/sANE treatments, and the COX-2 up-regulation might be mostly elicited from alternative nuclear factor-KB 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

The -765G>C Polymorphism in the Cyclooxygenase-2 Gene and Digestive System Cancer: a Meta-analysis

“…Evidence suggests that COX-2 plays an key role in the carcinogenesis pathway, such as in the inhibition of apoptosis, tumor growth, angiogenesis, invasion and metastasis (Leahy et al, 2000;Tatsuguchi et al, 2004;Wang et al, 2007;Gu et al, 2012;Huang et al, 2013;Saad et al, 2013), which are all crucial to many cancers, especially those belonging to the gastrointestinal tract, such as oral cancer (Chiang et al, 2008), gastric cancer (Liu et al, 2006), esophageal cancer (Kristinsson et al, 2009;Upadhyay et al, 2009), and colorectal cancer (Cox et al, 2004).…”

“…Thus, a final total of 38 case-control studies in 37 articles which met our inclusion criteria were identified, including 10814 cases and 16174 controls. Among 38 cases and controls, there were 20 case-controls of Asians (Hamajima et al, 2001;Koh et al, 2004;Liu et al, 2006;Guo et al, 2007;Tan et al, 2007;Chiang et al, 2008;Lin et al, 2008;Saxena et al, 2008;Ueda et al, 2008;Xing et al, 2008;Xu et al, 2008;Tang et al, 2009;Upadhyay et al, 2009;Zhao et al, 2009;Mittal et al, 2010;He et al, 2011;Chang et al, 2012;Li et al, 2012;Shin et al, 2012), 11 of Caucasians (Cox et al, 2004;Pereira et al, 2006;Hou et al, 2007;Moons et al, 2007;Sitarz et al, 2008;Andersen et al, 2009;Hoff et al, 2009;Iglesias et al, 2009;Kristinsson et al, 2009;Pereira et al, 2010;Daraei et al, 2012), 4 of Americans (Ulrich et al, 2005;Gunter et al, 2006;Gong et al, 2009;Thompson et al, 2009), and 1 of Africans (Bye et al, 2011), and 2 of Mixed (Bye et al, 2011;Wang et al, 2012). 9 investigated gastric cancer (Liu ...…”

“…9 investigated gastric cancer (Liu et al, 2006;Pereira et al, 2006;Hou et al, 2007;Saxena et al, 2008;Sitarz et al, 2008;Tang et al, 2009;Li et al, 2012;Shin et al, 2012), 16 investigated colorectal cancer (Hamajima et al, 2001;Cox et al, 2004;Koh et al, 2004;Ulrich et al, 2005;Gunter et al, 2006;Xing et al, 2008;Ueda et al, 2008;Andersen et al, 2009;Gong et al, 2009;Hoff et al, 2009;Iglesias et al, 2009;Thompson et al, 2009;Pereira et al, 2010;Daraei et al, 2012;Wang et al, 2012), 3 investigated oral cancer (Chiang et al, 2008;Lin et al, 2008;Mittal et al, 2010), 6 investigated esophageal cancer (Guo et al, 2007;Moons et al, 2007;Kristinsson et al, 2009;Upadhyay et al, 2009;Bye et al, 2011), and 4 investigated pancreatic cancer and hepatocellular carcinoma (HCC) (Xu et al, 2008;Zhao et al, 2009;He et al, 2011;Chang et al, 2012). Of these articles, 18 studies were performed in HB (Hamajima et al, 2001;Cox et al, 2004;Gunter et al, 2006;Pereira et al, 2006;…”

Arachidonic Acid Metabolism and Its Implication on Head and Neck Cancer

“…Upregulation of COX-2 has been reported in human tissues and cell lines as well as in serum of patients with HNC. The increased levels of COX-2 were associated with the risk of tobacco-and betel nutrelated cancers, advance clinical stage, survival and lymph node metastasis (Tang et al, 2003;Molinolo et al, 2007;Chiang et al, 2008;Husvik et al, 2009;Saba et al, 2009;Mittal et al, 2010). In addition, PGE 2 receptors are widely expressed in a variety of HNSCC cell lines as well as in tumor tissues (Abrahao et al, 2010).…”

Betel‐quid dependence domains and syndrome associated with betel‐quid ingredients among chewers: anAsian multi‐country evidence

“…Research findings by the International Agency for Research on Cancer have indicated that both tobaccoadded BQ (TA-BQ) and tobacco-free BQ (TF-BQ) are carcinogenic to humans [1,2,8]. Carcinomas of the upper aerodigestive tract are the primary neoplasms associated with their consumption [1,2,[8][9][10][11][12][13][14]. Large-scale epidemiological studies have reported that prolonged TF-BQ use is related to obesity, metabolic syndrome and adverse pregnancy outcomes [15][16][17].…”