Tricyclic antidepressants as risks factors for cancer

三环类抗抑郁药是癌症的危险因素

• 批准号: 6514986
• 负责人: JEAN-PAUL COLLET
• 金额: $ 8.79万
• 依托单位: SIR MORTIMER B. DAVIS JEWISH GEN HOSP
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6514986
• 关键词: cancer registry /resource; cancer risk; cell proliferation; chemical carcinogen; chemical carcinogenesis; drug administration rate /duration; drug related neoplasm /cancer; human data; neoplasm /cancer epidemiology; tricyclic antidepressant

DESCRIPTION: Rational and Aims: Although mechanisms have not been confirmed, animal and epidemiological studies suggest that antidepressants promote tumor growth in humans. Recently, a study in animals showed that tricyclic antidepressants (TCAs) with a nitrogen atom at position 5 in the 7-membered ring of their chemical structure (5-N) were genotoxic, as compared to those with a carbon atom at the same position (5-C) (Van Schaik et al. Mutation Research 1993, 286(2): 155-163). These results were confirmed in humans by a large epidemiologic study (Sharpe et al. submitted to the British Journal of Cancer, 2000). In this historical population-based case-control study we will investigate the effect of past exposure to 5-N TCAs on the risk of developing cancer at 19 different sites. Methods: The source population for the study will be the dynamic cohort defined by membership in the Saskatchewan Prescription Drug Plan (SPDP). Incident cancer cases (at one of the 19 sites considered) over 5 years of age will be accrued by the provincial cancer registry from 1981 to 1999. At least 4 controls/case will be selected from the source population, matched on age, gender, and calendar time, using incidence density sampling. Detailed drug exposure data over a minimum of 5 years before diagnosis and up to a maximum of 23 years will be obtained from the SPDP. We will study for each drug and each site the respective effects of dosage, timing of use, and duration of use. Significance: If the results show that long-term use of antidepressants affect the incidence of cancer, they will be relevant to clinicians (with an elaboration on the risk/benefit profile of this therapy) and to the pharmaceutical industry (with a view to modifying the structure of drugs to enhance their beneficial effects and to reduce their harmful effects).

描述：理由和目的：虽然机制尚未得到证实， 动物和流行病学研究表明，抗抑郁药促进肿瘤 人类的成长。最近，一项动物研究表明，三环 在一些实施方案中，本发明涉及在7-元环中的5位具有氮原子的抗抑郁剂（TCAs）， 其化学结构（5-N）的环是遗传毒性，相比之下， 在相同位置具有碳原子（5-C）（货车Schaik等人，Mutation Research 1993，286（2）：155-163）。这些结果在人类中得到了证实， 一项大型流行病学研究（Sharpe等人提交给《英国医学杂志》， Cancer，2000）。在这项历史性的基于人群的病例对照研究中，我们将 研究过去暴露于5-N TCA对发生以下风险的影响： 19个不同部位的癌症 方法：研究的源人群将是定义的动态队列 萨斯喀彻温省处方药计划（SPDP）事件 5岁以上的癌症病例（在考虑的19个地点之一）将被 省癌症登记处1981年至1999年累计的死亡人数。至少4 对照/病例将从源人群中选择，年龄匹配， 性别和日历时间，采用发病密度抽样。详细药物 诊断前至少5年和最多5年的暴露数据 从SPDP获得23年。我们将研究每种药物， 现场的剂量，使用时间和使用持续时间的各自影响。 意义：如果结果显示长期使用抗抑郁药影响 癌症的发病率，他们将与临床医生（与 对该疗法的风险/获益特征的阐述）和 制药工业（以改变药物结构， 加强其有益影响，减少其有害影响）。

项目成果

Antidepressants and risk of prostate cancer: a nested case-control study.

抗抑郁药和前列腺癌的风险：一项巢式病例对照研究。

• DOI: 10.1038/sj.pcan.4501003
• 发表时间: 2008
• 期刊: Prostate cancer and prostatic diseases
• 影响因子: 4.8
• 作者: Tamim,HM;Mahmud,S;Hanley,JA;Boivin,J-F;Stang,MR;Collet,J-P
• 通讯作者: Collet,J-P

Risk of breast cancer in association with exposure to two different groups of tricyclic antidepressants.

乳腺癌风险与接触两组不同的三环类抗抑郁药有关。

• DOI: 10.1002/pds.1233
• 发表时间: 2006
• 期刊: Pharmacoepidemiology and drug safety
• 影响因子: 2.6
• 作者: Tamim,Hani;Boivin,Jean-Francois;Hanley,James;Stang,Maryrose;Collet,Jean-Paul
• 通讯作者: Collet,Jean-Paul