过度肥胖带来癌症,三大理由佐证
2015/11/27
《柳叶刀》曾发布了超重和肥胖的人患上10类癌症的概率比普通人显著提高。那么,关键的问题来了,脂肪如何增加癌症的风险?本文综述了三大理由解释多余脂肪提高患癌风险。


肥胖是关于健康的经久不衰的话题,据世界肥胖联合会的报告,未来10年,全球将有1.777亿名成年人严重肥胖。肥胖会引发一系列健康问题,包括心脏病、中风、二型糖尿病和癌症等。据外媒报道,世界正面临肥胖危机,且每年将近50万癌症病例与肥胖有关,肥胖在美国肥胖将很快超过烟草成为癌症的首要因素。

过度肥胖带来10类癌症

2014年《柳叶刀》杂志上有研究揭示了超重和肥胖者患癌症的概率比普通人显著提高。研究人员统计了英国每年因肥胖导致的12000例癌症,并且预计肥胖人群患癌比例将以每年3700例的速度增长。该研究揭示了肥胖与以下10类癌症的关联度:


脂肪不只是一种填料,它更是一个器官

脂肪在体内主要有两个角色。首先脂肪在体内以脂质的形式储存热量,当食物稀缺时可作为备用能源,但如今大多数人摄入的能量超过其所消耗的,从而导致超重或肥胖的发生。其次脂肪在体内还有第二大功能——脂肪本质上是一个巨大的腺体,可发送生物信号和指令来影响身体的其他部位,这有助于控制生长、代谢及生殖周期等过程。也正是由于脂肪拥有开启和关闭生物过程的功能,因而其发送出的信号也存在黑暗的一面,特别是当人体超重或肥胖时,多余的脂肪会对健康有负面影响。

三大理由解释肥胖为何致癌

然而,目前公众对肥胖与癌症的关联意识还比较低,大约10个人中只有一个人认为肥胖会提高患癌几率。然而更严重的问题是脂肪如何增加癌症的风险?虽然有一些似是而非的解释,但研究人员也正在努力研究其中的缘由。如下为三大理论解释多余的脂肪如何导致癌症,每个理论背后均有科学依据。

理论一:与雌激素相关

肥胖与癌症最明显的关联体现在绝经后超重或肥胖的女性患子宫癌和乳腺癌的概率增加,这与雌激素水平升高有关。在绝经前,雌激素主要由卵巢细胞产生,但脂肪细胞也可产生雌激素。绝经后,卵巢停止供应雌激素,脂肪变成了激素的主要来源,且有研究证实绝经后肥胖可导致女性雌激素水平升高。

世界癌症基金会饮食与癌症专家Martin Wiseman教授对女性绝经后脂肪细胞生产雌激素增加乳腺癌和子宫癌的风险十分赞同,他表示,“雌激素引发癌症已十分了然,雌激素使某些细胞如乳腺细胞和子宫细胞分裂,因此过多的雌激素会引导细胞过度分裂,而不受控制的细胞分裂是癌症发展的根源。”

Wiseman教授进一步解释道,“大多关于女性的研究都显示了肥胖、高雌激素水平与乳腺癌和子宫癌有关联,理解这其中的关联对发展有效的治疗方法非常重要,例如三苯氧胺和芳香化酶抑制剂可通过切断雌激素来起作用。此外,如果给予乳腺癌高风险的女性以雌激素封阻疗法,将可减缓疾病的发展,切断雌激素可达到阻止乳腺癌发展的目的。”

雌激素与女性癌症的关联程度很强,但也有数据表明 ,肥胖导致的性激素变化在男性癌症中也发挥了作用,虽然这比较罕见,但有证据表明多余脂肪产生的雌激素与男性乳腺癌相关。同时,肥胖与侵略性前列腺癌也有关联,但目前尚不清楚这是否与脂肪细胞引起雌激素的变化有关,或者脂肪细胞可导致睾丸激素的变化?

理论二:代谢混乱

人体内的新陈代谢依赖于细胞与器官之间精密的信息流,并受到严格的控制。然而脂肪细胞可产生化学信号这意味着脂肪细胞可打破人体新陈代谢的平衡,而这被认为是导致癌症的原因之一。胰岛素是控制代谢的关键激素,但胰岛素指令可被血液中的化学物质如游离脂肪酸打乱,而高脂肪饮食则是影响游离脂肪酸的主要因素,不仅如此,体内尤其是腹部堆积的脂肪也可释放游离脂肪酸,这增加了对胰岛素的抵抗能力。

Wiseman教授对此表示,“胰岛素代谢混乱会导致各种问题,例如导致细胞对胰岛素产生抵抗性,胰腺对此做出反应并导致血糖水平下降。长期提高胰岛素水平可能是肥胖增加癌症风险的另一个因素。高水平胰岛素影响细胞生长因子水平的生长,胰岛素和这些生长因子都可能是导致癌症的危险因素,生长因子是细胞分裂的绿色信号。”

“有大量的实验证实了这种关联性:大量数据显示当癌细胞对胰岛素及与胰岛素相关的生长因子做出应答时,它们将变得更难对付且繁殖更快。对人体血液化学的研究显示了高水平葡萄糖与几种癌症之间的风险相关”,Wiseman教授表示。

综上所述,代谢混乱导致癌症很有说服力。然而最大的问题是它在肥胖人群癌症增长率中的作用程度有多大,目前研究人员也在开展这方面的研究。

理论三:炎症


随着人体脂肪的堆积,专门的免疫细胞(巨噬细胞)可清理死亡的脂肪细胞。但巨噬细胞在进行清理工作的过程也释放出强大的化学物质——细胞因子,以召唤其他细胞的帮助。脂肪组织中巨噬细胞的数量十分庞大,几乎10个细胞中就有4个是巨噬细胞,这将最终创建一个慢性炎症的条件,从另一角度来说肥胖可能是癌症发展的原料

许多慢性炎症及慢性炎症引发的感染可增加一个人患癌症的风险,今年发表于PNAS上的一则研究揭示了慢性炎症引发癌症的机制。免疫系统通过一些活性分子如氧化氢、一氧化氮或次氯酸等中和入侵者来消除炎症。然而,这些分子会间接损害周围健康组织。研究人员在研究中发现当小鼠感染肝螺杆菌后,发炎组织的DNA出现一种结构损害(5-chlorocytosine,5ClC)。这种损伤由免疫系统的次氯酸分子引起,导致DNA中的胞嘧啶受损。更重要的是5ClC损伤十分常见,且出现在50%与癌症有关的突变中。

Wiseman教授解释到,“炎症可给细胞分裂发出信号,因为受伤后需要新的细胞来愈合伤口,但鼓励细胞生长的信号同时也支持癌细胞分裂。事实上,如果我们观察炎症组织中控制开启和关闭的基因,我们会看到很多与癌细胞基因相关的变化。消炎药阿司匹林可预防肠癌,同时其他消炎药也可能预防其他类型的癌症,虽然这不能作为炎症引发癌症的确凿证据,但为此类研究指了一个方向。”

小结

毋庸置疑,肥胖与癌症存在关联,但其引发机制相当复杂。肥胖影响我们生理的诸多方面,包括激素、生长信号和炎症等。同时肥胖对每个人的影响也有差异,并不是每个肥胖者都会出现代谢异常或慢性炎症。

让事情更加复杂的是在超重或肥胖者体内雌性激素、胰岛素和炎症交织在一起,形成一个致命的织物影响着他们的身体健康。虽然很难理解这些因素是如何交织在一起,但研究人员发现一些有前景的治疗途径,通过研发阻断脂肪细胞信号的药物来防止癌症,例如目前正在研究是否可将二甲双胍和阿司匹林作为抗癌药物。肥胖不仅与癌症有关,同时还是其他重要疾病——糖尿病、心脏病和中风等罪魁祸首,因此肥胖问题不容忽视。

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