Pathophysiological mechanisms linking obesity and esophageal adenocarcinoma.
Pathophysiological mechanisms linking obesity and esophageal adenocarcinoma.
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DOI：
10.4291/wjgp.v5.i4.534
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发表时间：
2014-11-15
期刊：
影响因子：
--
通讯作者：
Beales, Ian Lp
中科院分区：
文献类型：
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作者：
Alexandre, Leo;Long, Elizabeth;Beales, Ian Lp
近几十年来，发达国家食管腺癌（EAC）的发病率急剧上升。大约在同一时期，肥胖症的流行率也有所增加。肥胖，尤其是内脏肥胖，是胃食管反流病、Barrett食管和EAC发生的重要独立危险因素。虽然最简单的解释是，这是由腹部肥胖促进胃食管反流的机械效应介导的，但流行病学数据表明，EAC促进效应与反流无关。几种并非相互排斥的机制已经被牵连，它们可能在反流-巴雷特癌症通路的沿着的不同点上具有不同的作用。这些机制包括降低幽门螺杆菌感染的患病率，通过增加胃饥饿素分泌来增强胃酸和可能的食欲，通过脂肪组织分泌的因子诱导低度全身性炎症和具有胰岛素抵抗的代谢综合征。肥胖与脂肪组织的瘦素分泌增加和脂联素分泌减少相关，瘦素增加和脂联素减少均被证明是进展为EAC的独立风险因素。瘦素和脂联素对巴雷特细胞具有一系列相互拮抗作用，这似乎影响恶性行为的进展。目前，没有药物被证明对预防肥胖相关的EAC有益。Roux-en-Y重建是反流患者体重减轻的首选减肥手术选择。他汀类药物和阿司匹林可能具有化学预防作用，并具有循环益处。
In recent decades there has been a dramatic rise in the incidence of esophageal adenocarcinoma (EAC) in the developed world. Over approximately the same period there has also been an increase in the prevalence of obesity. Obesity, especially visceral obesity, is an important independent risk factor for the development of gastro-esophageal reflux disease, Barrett's esophagus and EAC. Although the simplest explanation is that this mediated by the mechanical effects of abdominal obesity promoting gastro-esophageal reflux, the epidemiological data suggest that the EAC-promoting effects are independent of reflux. Several, not mutually exclusive, mechanisms have been implicated, which may have different effects at various points along the reflux-Barrett's-cancer pathway. These mechanisms include a reduction in the prevalence of Helicobacter pylori infection enhancing gastric acidity and possibly appetite by increasing gastric ghrelin secretion, induction of both low-grade systemic inflammation by factors secreted by adipose tissue and the metabolic syndrome with insulin-resistance. Obesity is associated with enhanced secretion of leptin and decreased secretion of adiponectin from adipose tissue and both increased leptin and decreased adiponectin have been shown to be independent risk factors for progression to EAC. Leptin and adiponectin have a set of mutually antagonistic actions on Barrett's cells which appear to influence the progression of malignant behaviour. At present no drugs are of proven benefit to prevent obesity associated EAC. Roux-en-Y reconstruction is the preferred bariatric surgical option for weight loss in patients with reflux. Statins and aspirin may have chemopreventative effects and are indicated for their circulatory benefits.