TNF and cancer: Despite this complexity, the large majority of studies on the biological mechanisms of cancer-related fatigue have focused on immune and inflammatory variables, which are hypothesized to induce fatigue via the effect of inflammatory mediators on brain systems involved in “sickness behaviors.” Specific variants include genes regulating inflammation (e.g., IL6, TNFA, and IL1) [29], inflammatory gene expression profiles (e.g., increased NF-kB) [30,31,32], and circulating markers of inflammation (e.g., IL-1, TNFA, CRP, and IL-6) [32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53].