Is norepinephrine an etiological factor in some types of cancer?

I examine evidence that the signaling molecule norepinephrine (NE) is an etiological factor in some types of cancer. In support of this hypothesis, I cite the following 7 lines of evidence: (i) rodent studies of tumorigenesis in the context of NE manipulation; (ii) human studies of tricyclic antidepressant use and cancer rate; (iii) existence of pheochromocytoma, a cancer of the adrenal glands; (iv) cancer rate in families with individuals who have bipolar disorder; (v) hypertension and cancer risk; (vi) excessive body weight and cancer risk; and (vii) psychological stressors and cancer risk. Three aspects of the body's NE system are consistent with it playing an etiological role in various types of cancer: (i) NE circulates in the blood and can thereby access organ systems throughout the body, in addition to direct peripheral release by the sympathetic nervous system and being released within the brain; (ii) many of the body's organs possess NE receptors on the outer surface of at least some of their cells; (iii) by binding to its extracellular receptors, NE affects intracellular second messenger systems that could influence carcinogenesis. Most importantly, use of existing pharmaceutical drugs that either lower the level of NE (such as clonidine) or block NE receptors may lower the probability of an individual developing cancer, and this hypothesis could be tested immediately by an epidemiologist through examination of existing medical records. Copyright 2008 Wiley-Liss, Inc.