Clinic for Pediatrics I, University Hospital Halle (Saale), Ernst-Grube-Str. 40, 06120, Halle (Saale), Germany.
Institute of Anatomy and Cell Biology, Medical Faculty of Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
Curr Obes Rep. 2020 Sep;9(3):204-212. doi: 10.1007/s13679-020-00387-w.
The purpose of this review is to summarize our current understanding of the association between childhood obesity and cancer risk later in life.
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-γ (IFN-γ), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α), 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.
本文旨在总结目前对儿童肥胖与成年后癌症风险之间关联的认识。
脂肪组织分泌多种脂肪细胞因子，其中大多数的表达和/或分泌率似乎在肥胖时增加或失调。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，促进炎症免疫细胞浸润脂肪组织。这一过程可能促进“亚临床炎症”（代谢炎症）的发生，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，一些癌基因已通过不同途径与炎症和癌症发展相关联，几种类型的肿瘤在发生恶性转化之前需要炎症环境。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）细胞在这个过程中起着重要作用，因为它们能够在没有预先致敏的情况下杀死转化细胞，并通过产生独特的细胞因子来协调随后的免疫反应，从而提供抗肿瘤免疫。对儿童的初步研究表明，肥胖儿童的 NK 细胞被激活、代谢应激和功能缺陷。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）与成年后患多种恶性肿瘤的风险增加之间存在很强的关联，包括白血病、霍奇金病、结直肠癌和乳腺癌。其潜在机制尚不完全清楚，但几种脂肪细胞因子和炎症标志物，包括 NK 细胞，似乎是这一过程中的“关键因素”。
