The inflammatory inception of gallbladder cancer

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• 作者：Jaime A. Espinoza^a ; Carolina Bizama^b ; Patricia Garcí ; a^b ; Catterina Ferreccio^c ; Milind Javle^d ; Juan F. Miquel^e ; Jill Koshiol^f ; Juan C. Roa^b ; ^{jcroa@med.puc.cl" class="auth_mail" title="E-mail the corresponding author}
• 关键词：GBC ; gallbladder cancer ; GSD ; gallstone disease ; PTGS2 (COX-2) ; prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) ; AAPBD ; anomalous arrangement of the pancreaticobiliary duct ; PSC ; primary sclerosing cholangitis ; LXRs ; Liver X Receptors ; NSAID ; nonsteroidal anti-inflammatory drug
• 刊名：Biochimica et Biophysica Acta (BBA)-Reviews on Cancer
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：1865
• 期：2
• 页码：245-254
• 全文大小：2108 K

文摘

Gallbladder cancer is a lethal disease with notable geographical variations worldwide and a predilection towards women. Its main risk factor is prolonged exposure to gallstones, although bacterial infections and other inflammatory conditions are also associated. The recurrent cycles of gallbladder epithelium damage and repair enable a chronic inflammatory environment that promotes progressive morphological impairment through a metaplasia–dysplasia–carcinoma, along with cumulative genome instability. Inactivation of TP53, which is mutated in over 50% of GBC cases, seems to be the earliest and one of the most important carcinogenic pathways involved. Increased cell turnover and oxidative stress promote early alteration of TP53, cell cycle deregulation, apoptosis and replicative senescence. In this review, we will discuss evidence for the role of inflammation in gallbladder carcinogenesis obtained through epidemiological studies, genome-wide association studies, experimental carcinogenesis, morphogenetic studies and comparative studies with other inflammation-driven malignancies. The evidence strongly supports chronic, unresolved inflammation as the main carcinogenic mechanism of gallbladder cancer, regardless of the initial etiologic trigger. Given this central role of inflammation, evaluation of the potential for GBC prevention removing causes of inflammation or using anti-inflammatory drugs in high-risk populations may be warranted.