Ozerdem Aysegul, Ceylan Deniz, Targıtay Bilge
Department of Psychiatry, School of Medicine, Dokuz Eylul University, Izmir, Turkey.
Department of Neuroscience, Health Sciences Institute, Dokuz Eylul University, Izmir, Turkey.
Curr Drug Metab. 2018;19(8):653-662. doi: 10.2174/1389200219666180430095933.
The incidence and mortality rates of cancer in patients with Bipolar Disorder (BD) is higher compared with the general population. The role of Lithium (Li) in cancer proliferation/inhibition is still a controversial issue in the literature.
Based on a clinical case with lithium intake and development of a renal tumor, we aimed to explore the relationship between Li use and tumor proliferation, with regard to the mechanism of action of Li.
We present evidence of a female patient with bipolar disorder I, who had been on Li for several years, either as monotherapy or in combination with Valproate (VPA). While on Li monotherapy, the patient had undergone unilateral nephrectomy due to a chromophobe cell renal tumor. A literature search was performed using keywords bipolar disorder, medical comorbidity, cancer, renal tumor, lithium, mood stabilizers, valproate and mechanism of action.
The limited data on the relationship between Li and cancer proliferation in clinical populations support neither a positive relationship between long-term Li use and increased urinary tract cancers nor an overall cancer risk. Growing evidence identifies effects of Li on cancer proliferation through inhibition of glycogen synthase kinase-3β (GSK-3β), modulations of redox status, inflammatory changes, pro-/anti-apoptotic mechanisms, and mitochondrial function changes.
Despite the presence of contradictory data, a substantial body of evidence mainly from molecular studies points to Li's anti-carcinogenic effects. However, the underlying mechanistic pathways remain unclear. Mitochondrial dysfunction and redox modulations are potential areas for research on the relationship between Li and cancer proliferation.
双相情感障碍（BD）患者的癌症发病率和死亡率高于普通人群。锂（Li）在癌症增殖/抑制中的作用在文献中仍是一个有争议的问题。
基于一例服用锂并发生肾肿瘤的临床病例，我们旨在探讨锂的使用与肿瘤增殖之间的关系，以及锂的作用机制。
我们提供了一名患有I型双相情感障碍女性患者的证据，该患者多年来一直服用锂，单独使用或与丙戊酸盐（VPA）联合使用。在单独使用锂治疗期间，该患者因嫌色细胞肾肿瘤接受了单侧肾切除术。使用双相情感障碍、合并症、癌症、肾肿瘤、锂、心境稳定剂、丙戊酸盐和作用机制等关键词进行了文献检索。
临床人群中关于锂与癌症增殖之间关系的有限数据既不支持长期使用锂与尿路癌症增加之间的正相关关系，也不支持总体癌症风险。越来越多的证据表明，锂通过抑制糖原合酶激酶-3β（GSK-3β）、调节氧化还原状态、炎症变化、促凋亡/抗凋亡机制以及线粒体功能变化来影响癌症增殖。
尽管存在相互矛盾的数据，但大量主要来自分子研究的证据表明锂具有抗癌作用。然而，潜在的机制途径仍不清楚。线粒体功能障碍和氧化还原调节是研究锂与癌症增殖关系的潜在领域。
