Childhood Obesity and Cancer Risk in Adulthood

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.