Fitzgerald Paul J
Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore, MD 21218, USA.
Int J Cancer. 2009 Jan 15;124(2):257-63. doi: 10.1002/ijc.24063.
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.
信号分子去甲肾上腺素(NE)是某些类型癌症的病因。为支持这一假设,我列举了以下7条证据:(i)在NE调控背景下对啮齿动物肿瘤发生的研究;(ii)对使用三环类抗抑郁药与癌症发病率的人体研究;(iii)嗜铬细胞瘤(一种肾上腺癌症)的存在;(iv)有双相情感障碍患者的家族中的癌症发病率;(v)高血压与癌症风险;(vi)超重与癌症风险;以及(vii)心理应激源与癌症风险。人体NE系统的三个方面与其在各类癌症中发挥病因学作用相一致:(i)NE在血液中循环,因此除了由交感神经系统直接在外周释放以及在脑内释放外,还能够进入全身的器官系统;(ii)人体的许多器官在其至少部分细胞的外表面具有NE受体;(iii)通过与其细胞外受体结合,NE影响可能会影响致癌作用的细胞内第二信使系统。最重要的是,使用能够降低NE水平(如可乐定)或阻断NE受体的现有药物可能会降低个体患癌的概率,并且这一假设可由流行病学家通过查阅现有医疗记录立即进行检验。