Life style and psychosocial factors, vagal nerve activity and risk of future cancer
"Cancer is a multifactorial fatal disease and among the major causes of morbidity and mortality worldwide. Despite this, progress has taken place over the recent years in the screening, early detection and treatment of certain cancers such as breast cancer. However, a great deal of progress needs to be done in the prevention of this disease. Indeed, improving one’s life style habits such as increase in the Mediterranean diet (Milajerdi et al., 2018) and increase in physical activity (Baumeister et al., 2019) predict reduced risk of developing cancer. However, rather than focusing on single risk or protective factors, greater progress in cancer prevention could be possibly achieved by harnessing a protective factor which is related to the basic biological processes causing cancer, which predicts a lower risk of cancer and which is also related to life style factors. We recently proposed that the vagal nerve meets all three criteria for several chronic diseases in general and for cancer specifically (Gidron et al., 2018). Furthermore, by identifying a protective factor which mediates (explains) or moderates (weakens) the etiological role of other risk factors, we may reduce the risk of cancer even more. Again, some evidence suggests that the vagus nerve may do this as well. Our team found that tumor stage predicts future tumor burden levels, but only in patients will little vagal activity, but not in those with higher vagal activity (Gidron et al., 2014).
Only a few psychosocial factors predict risk of cancer, but more predict cancer prognosis (Chida et al., 2008). Job stress, an important psychosocial factor, was found in a recent meta-analysis to predict risk of certain cancers (e.g., colon, lung; Yang et al., 2019)). Hundreds of studies have shown that environmental factors such as cigarette smoking and insufficient physical activity predict risk of several cancers (e.g., Emilio et al., 2019; Oruc & Kaplan 2019). Based on the following rationale and converging evidence, we hereby propose that the vagal nerve may mediate (explain) and moderate (weaken) the effects of such risk factors on cancer-risk. Anatomically and physiologically, the vagal nerve mediates and modulates multiple physiological signals between the viscera and the brain such as peripheral inflammation (Tracey, 2009). Furthermore, the vagus nerve may reduce cancer risk because it inhibits inflammation, oxidative stress and sympathetic activity (De Couck et al., 2012; Gidron et al., 2005; Tracey, 2009), all promotors of carcinogenesis (e.g., (Mantovani et al., 2008)). Thus, vagal activity may mediate or moderate effects of lifestyle factors since these cause cancer also via oxidative stress (Moktar et al., 2011). Additionally, lifestyle factors are directly associated with vagal nerve activity (Gidron et al., 2018).
Concerning psychosocial variables, the vagus is a major part of the parasympathetic nervous system and its index, heart rate variability (HRV), is associated positively with frontal brain activity (Thayer et al., 2012). Furthermore, activating the vagus reduces negative psychological states including depression and anxiety (e.g., Hein et al., 2013). Epidemiologically, HRV independently predicts cancer survival, as shown in a meta-analysis and systematic review (De Couck et al., 2018; Zhou et al., 2016). However, it is unknown whether HRV itself predicts cancer-onset. Furthermore, it is unknown whether HRV statistically mediates (explains) or moderates (interacts with) effects of psychosocial or lifestyle factors in relation to cancer-onset. Finally, it is unknown whether reduced inflammation may explain why vagal activity predicts lower risk of cancer, as hypothesized for cancer prognosis (Gidron et al., 2005)."