Childhood Obesity and Cancer Risk in Adulthood
Childhood Obesity and Cancer Risk in Adulthood
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DOI：
10.1007/s13679-020-00387-w
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发表时间：
2020-06-09
影响因子：
8.8
通讯作者：
Weihrauch-Blueher, Susann
中科院分区：
文献类型：
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作者：
Weihe, Paul;Spielmann, Julia;Weihrauch-Blueher, Susann
综述的目的本综述的目的是总结我们目前对儿童肥胖和以后生活中癌症风险之间关系的理解。脂肪组织分泌多种脂肪细胞因子，其中大多数的表达和/或分泌速率似乎在肥胖中增加或失调。此外，肥胖导致促炎细胞因子如干扰素-γ（IFN-γ）、白细胞介素6（IL-6）和肿瘤坏死因子-α（TNF-α）的分泌增加，这促进炎性免疫细胞浸润到脂肪组织中。这一过程可能会促进“亚临床炎症”（metaflammation）的状态，并可能导致代谢综合征（MetS）的发展，早在儿童时期就开始了。此外，几种癌基因通过不同的途径与炎症和癌症发展有关，并且几种类型的肿瘤在恶性变化发生之前需要炎症环境。炎症环境似乎促进恶性细胞的增殖和存活以及血管生成。自然杀伤（NK）细胞在这一过程中发挥重要作用，因为它们能够杀死转化细胞而无需事先致敏，并通过产生不同的细胞因子协调随后的免疫应答，从而提供抗肿瘤免疫。儿童的第一项研究表明，肥胖儿童的NK细胞被激活，代谢紧张，功能缺陷。这可能导致早在儿童时期就抑制抗肿瘤免疫，可能在癌症发生前多年。流行病学研究表明，儿童和青少年时期较高的体重指数（BMI）与成年后几种恶性肿瘤（包括白血病、霍奇金病、结直肠癌和乳腺癌）的风险增加之间存在密切联系。潜在的机制尚未完全了解，但几种脂肪细胞因子和炎症标志物，包括NK细胞似乎是“关键球员”在这个过程中。
Purpose of Review The purpose of this review is to summarize our current understanding of the association between childhood obesity and cancer risk later in life. Recent Findings Adipose tissue secrets a variety of adipocytokines, and expression and/or secretion rate of most of them seems to be increased or dysregulated in obesity. In addition, obesity leads to increased secretion of proinflammatory cytokines such as interferon-gamma (IFN-gamma), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha), which promotes an infiltration of inflammatory immune cells into adipose tissue. This process may facilitate a state of "subclinical inflammation" (metaflammation) and may lead to the development of the metabolic syndrome (MetS), starting as early as during childhood. In addition, several oncogenes have been linked to inflammation and cancer development via different pathways, and several types of tumors need an inflammatory environment before a malignant change occurs. An inflammatory environment seems to promote the proliferation and survival of malignant cells as well as angiogenesis. Natural killer (NK) cells play an important role in this process, as they are able to kill transformed cells without prior sensitization and coordinate subsequent immune responses by producing distinct cytokines, thus providing antitumor immunity. First studies in children have suggested that NK cells from obese children are activated, metabolically stressed, and functionally deficient. This may lead to a suppression of antitumor immunity as early as during childhood, probably many years before the development of cancer. Epidemiological studies have shown a strong association between higher body mass index (BMI) during childhood and adolescence and increased risk for several malignancies in adulthood, including leukemia, Hodgkin's disease, colorectal cancer, and breast cancer. Underlying mechanisms are not completely understood, but several adipocytokines and inflammatory markers including NK cells seem to be "key players" in this process.