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Lee E, Park Y, Li D, Rodriguez-Fuguet A, Wang X, Zhang WC. Antidepressant Use and Lung Cancer Risk and Survival: A Meta-analysis of Observational Studies. CANCER RESEARCH COMMUNICATIONS 2023; 3:1013-1025. [PMID: 37377607 PMCID: PMC10259481 DOI: 10.1158/2767-9764.crc-23-0003] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Revised: 03/14/2023] [Accepted: 05/17/2023] [Indexed: 06/29/2023]
Abstract
Recent preclinical studies have linked antidepressants (AD) to their potential anticancer effects in multiple cancers, but the impact on lung cancer remains unclear. This meta-analysis examined the associations between ADs and lung cancer incidence and survival. The Web of Science, Medline, CINAHL, and PsycINFO databases were searched to identify eligible studies published by June 2022. We conducted a meta-analysis using a random-effects model to compare the pooled risk ratio (RR) and 95% confidence interval (CI) in those treated with or without ADs. Heterogeneity was examined using Cochran Q test and inconsistency I2 statistics. The methodologic quality of the selected studies was assessed using the Newcastle-Ottawa Scale for observational studies. Our analysis, including 11 publications involving 1,200,885 participants, showed that AD use increased lung cancer risk by 11% (RR = 1.11; 95% CI = 1.02-1.20; I2 = 65.03%; n = 6) but was not associated with overall survival (RR = 1.04; 95% CI = 0.75-1.45; I2 = 83.40%; n = 4). One study examined cancer-specific survival. Subgroup analysis showed that serotonin and norepinephrine reuptake inhibitors (SNRIs) were associated with an increased lung cancer risk by 38% (RR = 1.38; 95% CI = 1.07-1.78; n = 2). The quality of selected studies was good (n = 5) to fair (n = 6). Our data analysis suggests that SNRIs were associated with an elevated risk of lung cancer, raising concerns regarding the use of AD treatment in patients vulnerable to lung cancer. The effects of ADs-particularly SNRIs-and their interplay with cigarette use and lung cancer risk in vulnerable patients merits further study. Significance In this meta-analysis of 11 observational studies, we found evidence of a statistically significant association between the use of certain ADs and lung cancer risk. This effect merits further study, particularly as it relates to known environmental and behavioral drivers of lung cancer risk, such as air pollution and cigarette smoke.
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Affiliation(s)
- Eunkyung Lee
- Department of Health Sciences, College of Health Professions and Sciences, University of Central Florida, Orlando, Florida
| | - Yongho Park
- College of Medicine, University of Central Florida, Orlando, Florida
| | - David Li
- Department of Health Sciences, College of Health Professions and Sciences, University of Central Florida, Orlando, Florida
| | - Alice Rodriguez-Fuguet
- Department of Cancer Division, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida
| | - Xiaochuan Wang
- School of Social Work, College of Health Professions and Sciences, University of Central Florida, Orlando, Florida
| | - Wen Cai Zhang
- Department of Cancer Division, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida
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Cohen Sedgh R, Moon J, Jackevicius CA. Neoplasm Reports in Food and Drug Administration Adverse Event Reporting System Following Angiotensin Receptor Blocker Recalls. Circ Cardiovasc Qual Outcomes 2021; 14:e007476. [PMID: 34380327 DOI: 10.1161/circoutcomes.120.007476] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND A worldwide voluntary recall of valsartan in July 2018 due to the potential carcinogen N-nitrosodimethylamine received extensive media and public attention. This was followed by more Food and Drug Administration (FDA) recalls regarding other contaminated ARB (angiotensin receptor blocker) products. Our study investigated the association between the FDA recalls and ARB neoplasm adverse events (AEs) reported to the FDA adverse event reporting system. METHODS In this cross-sectional study, data were retrospectively collected from the FDA adverse event reporting system database from January 2015 to December 2019. Reporting odds ratios (RORs) were estimated to detect signals of association between ARBs (valsartan, irbesartan, and losartan) and reported neoplasm AEs using negative (amoxicillin and sertraline) and positive (omeprazole and ranitidine) control exposures. The χ2 was used to compare categorical variables. RESULTS A total of 2 181 524 AEs, including 10 461 nonmetastatic neoplasm AEs were analyzed. Monthly RORs (95% CI) of valsartan-associated neoplasms versus controls (ROR*: valsartan/negative exposures; ROR†: valsartan/omeprazole; and ROR‡: valsartan/ranitidine) showed the highest signals after the recall date in July 2018 (7.64 [4.78-12.19]*; 4.77 [3.36-6.79]†; 4.13 [2.50-6.84]‡) and August 2018 (7.87 [5.19-11.94]*; 5.65 [4.12-7.75]†; and 7.20 [4.46-11.63]‡). In contrast, the highest cancer signals for the irbesartan and losartan recalls detected in March 2019 (4.80*; 4.06†; and 3.38‡) and April 2019 (3.63*; 3.69†; and 2.52‡) respectively, were lower. One-year postrecall reported neoplasm AEs were ≈2-fold higher for valsartan than irbesartan (OR, 1.77 [95% CI, 1.47-2.13], P<0.0001) and losartan (OR, 2.07 [95% CI, 1.85-2.32], P<0.0001). Although all ARBs had the same nitrosamine contamination, we found 1-year postrecall versus prerecall cancer signals for valsartan were 3-fold higher versus control exposures, while the changes in RORs for irbesartan and losartan were only 20-30% higher. CONCLUSIONS Significantly more postrecall neoplasms were reported for valsartan, with higher valsartan-associated cancer signals compared with irbesartan and losartan, although they all contained the same carcinogenic contaminant. Extensive media coverage of the FDA valsartan recall may have alarmed patients and generated these abrupt, biologically infeasible cancer signals.
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Affiliation(s)
- Robert Cohen Sedgh
- Western University of Health Sciences, Pomona, CA (R.C.S., J.M., C.A.J.)
| | - Jungyeon Moon
- Western University of Health Sciences, Pomona, CA (R.C.S., J.M., C.A.J.)
| | - Cynthia A Jackevicius
- Western University of Health Sciences, Pomona, CA (R.C.S., J.M., C.A.J.).,VA Greater Los Angeles Healthcare System, CA (C.A.J.).,Institute for Clinical Evaluative Sciences, Toronto, Canada (C.A.J.).,Institute of Health Policy, Management and Evaluation, University of Toronto, Canada (C.A.J.)
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Combined Use of Aspirin and Selective Serotonin Reuptake Inhibitors Is Associated With Lower Risk of Colorectal Cancer: A Nested Case-Control Study. Am J Gastroenterol 2021; 116:1313-1321. [PMID: 33661146 DOI: 10.14309/ajg.0000000000001192] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Accepted: 01/22/2021] [Indexed: 12/24/2022]
Abstract
INTRODUCTION Chemoprevention against colorectal cancer (CRC) is greatly needed. As the development of CRC involves multiple dysfunctional pathways, it is thus reasonable to combine some agents that address several pathways to achieve better chemoprotection. We aimed to explore whether the use of aspirin and selective serotonin reuptake inhibitors (SSRIs)-either as monotherapy or combined-can have a clinical benefit against CRC. METHODS We performed a nested case-control study using nationwide Swedish registers. We recruited 24,786 CRC cases and randomly matched to 74,358 controls conditional on birth year and sex using incidence-density sampling. The conditional logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Additive interaction was calculated as the relative excess risk for interaction, and multiplicative interaction was calculated by including a product term in the regression model. RESULTS Both aspirin and SSRIs monotherapy were negatively associated with CRC risk, but the combined use of aspirin and SSRIs was associated with an even lower CRC risk (adjusted OR, 0.77, 95% CI, 0.67-0.89) than aspirin monotherapy (adjusted OR, 0.91, 95% CI, 0.87-0.97) or SSRI monotherapy (adjusted OR, 0.93, 95% CI, 0.86-1.00). A significant interaction was observed at the additive scale with a relative excess risk for interaction of -0.07 (P < 0.001), whereas no interaction was noted on the interactive scale. The inverse associations of CRC with aspirin and SSRIs showed a dose-dependent pattern. DISCUSSION This study suggests that the use of aspirin and SSRIs-either as monotherapy or combined-was associated with a reduced risk of CRC. The stronger chemoprevention of combined use of aspirin and SSRIs is innovative and calls for further studies to confirm the underlying mechanisms and the plausibility of clinical recommendation.
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Ye D, Xu H, Xia H, Zhang C, Tang Q, Bi F. Targeting SERT promotes tryptophan metabolism: mechanisms and implications in colon cancer treatment. J Exp Clin Cancer Res 2021; 40:173. [PMID: 34006301 PMCID: PMC8132442 DOI: 10.1186/s13046-021-01971-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 05/05/2021] [Indexed: 02/08/2023] Open
Abstract
Background Serotonin signaling has been associated with tumorigenesis and tumor progression. Targeting the serotonin transporter to block serotonin cellular uptake confers antineoplastic effects in various tumors, including colon cancer. However, the antineoplastic mechanism of serotonin transporter inhibition and serotonin metabolism alterations in the absence of serotonin transporter have not been elucidated, especially in colon cancer, which might limit anti-tumor effects associating with targeting serotonin transporter. Methods The promotion in the uptake and catabolism of extracellular tryptophan and targeting serotonin transporter was detected by using quantitative reverse-transcription polymerase chain reaction, western blotting and liquid chromatography tandem mass spectrometry. Western blotting Immunoprecipitation and immunofluorescence was utilized to research the serotonylation of mTOR by serotonin and serotonin transporter inhibition. The primary mouse model, homograft model and tissue microarry was used to explore the tryptophan pathway in colon cancer. The cell viability assay, western blotting, xenograft and primary colon cancer mouse model were used to identify whether the combination of sertraline and tryptophan restriction had a synergistic effect. Results Targeting serotonin transporter through genetic ablation or pharmacological inhibition in vitro and in vivo induced a compensatory effect by promoting the uptake and catabolism of extracellular tryptophan in colon cancer. Mechanistically, targeting serotonin transporter suppressed mTOR serotonylation, leading to mTOR inactivation and increased tryptophan uptake. In turn, this process promoted serotonin biosynthesis and oncogenic metabolite kynurenine production through enhanced tryptophan catabolism. Tryptophan deprivation, or blocking its uptake by using trametinib, a MEK inhibitor, can sensitize colon cancer to selective serotonin reuptake inhibitors. Conclusions The present study elucidated a novel feedback mechanism involved in the regulation of serotonin homeostasis and suggested innovative strategies for selective serotonin reuptake inhibitors-based treatment of colon cancer. Supplementary Information The online version contains supplementary material available at 10.1186/s13046-021-01971-1.
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Affiliation(s)
- Di Ye
- Department of Medical Oncology, Cancer Center and Laboratory of Molecular, Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Huanji Xu
- Department of Medical Oncology, Cancer Center and Laboratory of Molecular, Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Hongwei Xia
- Department of Medical Oncology, Cancer Center and Laboratory of Molecular, Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Chenliang Zhang
- Department of Medical Oncology, Cancer Center and Laboratory of Molecular, Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Qiulin Tang
- Department of Medical Oncology, Cancer Center and Laboratory of Molecular, Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Feng Bi
- Department of Medical Oncology, Cancer Center and Laboratory of Molecular, Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China.
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Dragioti E, Solmi M, Favaro A, Fusar-Poli P, Dazzan P, Thompson T, Stubbs B, Firth J, Fornaro M, Tsartsalis D, Carvalho AF, Vieta E, McGuire P, Young AH, Shin JI, Correll CU, Evangelou E. Association of Antidepressant Use With Adverse Health Outcomes: A Systematic Umbrella Review. JAMA Psychiatry 2019; 76:1241-1255. [PMID: 31577342 PMCID: PMC6777224 DOI: 10.1001/jamapsychiatry.2019.2859] [Citation(s) in RCA: 129] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
IMPORTANCE Antidepressant use is increasing worldwide. Yet, contrasting evidence on the safety of antidepressants is available from meta-analyses, and the credibility of these findings has not been quantified. OBJECTIVE To grade the evidence from published meta-analyses of observational studies that assessed the association between antidepressant use or exposure and adverse health outcomes. DATA SOURCES PubMed, Scopus, and PsycINFO were searched from database inception to April 5, 2019. EVIDENCE REVIEW Only meta-analyses of observational studies with a cohort or case-control study design were eligible. Two independent reviewers recorded the data and assessed the methodological quality of the included meta-analyses. Evidence of association was ranked according to established criteria as follows: convincing, highly suggestive, suggestive, weak, or not significant. RESULTS Forty-five meta-analyses (17.9%) from 4471 studies identified and 252 full-text articles scrutinized were selected that described 120 associations, including data from 1012 individual effect size estimates. Seventy-four (61.7%) of the 120 associations were nominally statistically significant at P ≤ .05 using random-effects models. Fifty-two associations (43.4%) had large heterogeneity (I2 > 50%), whereas small-study effects were found for 17 associations (14.2%) and excess significance bias was found for 9 associations (7.5%). Convincing evidence emerged from both main and sensitivity analyses for the association between antidepressant use and risk of suicide attempt or completion among children and adolescents, autism spectrum disorders with antidepressant exposure before and during pregnancy, preterm birth, and low Apgar scores. None of these associations remained supported by convincing evidence after sensitivity analysis, which adjusted for confounding by indication. CONCLUSIONS AND RELEVANCE This study's findings suggest that most putative adverse health outcomes associated with antidepressant use may not be supported by convincing evidence, and confounding by indication may alter the few associations with convincing evidence. Antidepressant use appears to be safe for the treatment of psychiatric disorders, but more studies matching for underlying disease are needed to clarify the degree of confounding by indication and other biases. No absolute contraindication to antidepressants emerged from this umbrella review.
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Affiliation(s)
- Elena Dragioti
- Pain and Rehabilitation Centre, Department of Medicine and Health Sciences, Linköping University, Linköping, Sweden,Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, University Campus, Ioannina, Greece
| | - Marco Solmi
- Department of Neuroscience, University of Padua, Padua, Italy,Padova Neuroscience Center (PNC), University of Padua, Padua, Italy,Early Psychosis: Interventions and Clinical-Detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
| | - Angela Favaro
- Department of Neuroscience, University of Padua, Padua, Italy,Padova Neuroscience Center (PNC), University of Padua, Padua, Italy
| | - Paolo Fusar-Poli
- Early Psychosis: Interventions and Clinical-Detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom,OASIS Service, South London and Maudsley NHS (National Health Service) Foundation Trust, London, United Kingdom,Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
| | - Paola Dazzan
- Section of Imaging, Neurobiology, and Psychosis, Department of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, United Kingdom,National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust, London, United Kingdom
| | - Trevor Thompson
- Department of Psychology, Social Work and Counselling, University of Greenwich, Greenwich, United Kingdom
| | - Brendon Stubbs
- Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, United Kingdom,Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
| | - Joseph Firth
- NICM Health Research Institute, School of Science and Health, University of Western Sydney, Sydney, Australia,Division of Psychology and Mental Health, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom,Centre for Youth Mental Health, University of Melbourne, Melbourne, Australia
| | - Michele Fornaro
- Department of Neuroscience, Reproductive Sciences and Dentistry, Federico II University, Naples, Italy
| | | | - Andre F. Carvalho
- Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
| | - Eduard Vieta
- Department of Psychiatry and Psychology, Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, the Spanish Ministry of Science and Innovation (CIBERSAM), Barcelona, Catalonia, Spain
| | - Philip McGuire
- Early Psychosis: Interventions and Clinical-Detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
| | - Allan H. Young
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom,South London and Maudsley NHS Foundation Trust, Bethlem Royal Hospital, Beckenham, Kent, United Kingdom
| | - Jae Il Shin
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Christoph U. Correll
- Department of Psychiatry, Zucker Hillside Hospital, Glen Oaks, New York,Department of Psychiatry and Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, New York,Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, New York,Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Department of Child and Adolescent Psychiatry, Berlin Institute of Health, Berlin, Germany
| | - Evangelos Evangelou
- Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, University Campus, Ioannina, Greece,Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom
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Sakita JY, Bader M, Santos ES, Garcia SB, Minto SB, Alenina N, Brunaldi MO, Carvalho MC, Vidotto T, Gasparotto B, Martins RB, Silva WA, Brandão ML, Leite CA, Cunha FQ, Karsenty G, Squire JA, Uyemura SA, Kannen V. Serotonin synthesis protects the mouse colonic crypt from DNA damage and colorectal tumorigenesis. J Pathol 2019; 249:102-113. [PMID: 31038736 DOI: 10.1002/path.5285] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2018] [Revised: 03/19/2019] [Accepted: 04/26/2019] [Indexed: 12/31/2022]
Abstract
Serotonin (5-HT) signaling pathways are thought to be involved in colorectal tumorigenesis (CRT), but the role of 5-HT synthesis in the early steps of this process is presently unknown. In this study, we used carcinogen treatment in the tryptophan hydroxylase 1 knockout (Tph1KO) and transgenic (Tph1fl/fl VillinCre ) mouse models defective in 5-HT synthesis to investigate the early mutagenic events associated with CRT. Our observations of the colonic crypt post-treatment followed a timeline designed to understand how disruption of 5-HT synthesis affects the initial steps leading to CRT. We found Tph1KO mice had decreased development of both allograft tumors and colitis-related CRT. Interestingly, carcinogenic exposure alone induced multiple colon tumors and increased cyclooxygenase-2 (Ptgs2) expression in Tph1KO mice. Deletion of interleukin 6 (Il6) in Tph1KO mice confirmed that inflammation was a part of the process. 5-HT deficiency increased colonic DNA damage but inhibited genetic repair of specific carcinogen-related damage, leading to CRT-related inflammatory reactions and dysplasia. To validate a secondary effect of 5-HT deficiency on another DNA repair pathway, we exposed Tph1KO mice to ionizing radiation and found an increase in DNA damage associated with reduced levels of ataxia telangiectasia and Rad3 related (Atr) gene expression in colonocytes. Restoring 5-HT levels with 5-hydroxytryptophan treatment decreased levels of DNA damage and increased Atr expression. Analysis of Tph1fl/fl VillinCre mice with intestine-specific loss of 5-HT synthesis confirmed that DNA repair was tissue specific. In this study, we report a novel protective role for 5-HT synthesis that promotes DNA repair activity during the early stages of colorectal carcinogenesis. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Affiliation(s)
- Juliana Y Sakita
- Department of Toxicology, Bromatology, and Clinical Analysis, University of Sao Paulo, Ribeirao Preto, Brazil
| | - Michael Bader
- Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Canada.,Charité, University Medicine Berlin, Berlin, Germany.,Berlin Institute of Health (BIH), Berlin, Germany
| | - Emerson S Santos
- Department of Toxicology, Bromatology, and Clinical Analysis, University of Sao Paulo, Ribeirao Preto, Brazil
| | - Sergio B Garcia
- Department of Pathology, University of Sao Paulo, Ribeirao Preto, Brazil
| | - Stefania B Minto
- Department of Pathology, University of Sao Paulo, Ribeirao Preto, Brazil
| | - Natalia Alenina
- Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Canada.,Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia
| | | | - Milene C Carvalho
- Faculty of Philosophy, Sciences and Letters, University of São Paulo, Ribeirao Preto, Brazil
| | - Thiago Vidotto
- Department of Genetics, University of Sao Paulo, Ribeirao Preto, Brazil
| | - Bianca Gasparotto
- Department of Toxicology, Bromatology, and Clinical Analysis, University of Sao Paulo, Ribeirao Preto, Brazil
| | - Ronaldo B Martins
- Department of Cell and Molecular Biology, Virology Research Center, University of Sao Paulo, Ribeirao Preto, Brazil
| | - Wilson A Silva
- Department of Genetics, University of Sao Paulo, Ribeirao Preto, Brazil
| | - Marcus L Brandão
- Faculty of Philosophy, Sciences and Letters, University of São Paulo, Ribeirao Preto, Brazil
| | - Caio A Leite
- Department of Pharmacology, University of Sao Paulo, Ribeirao Preto, Brazil
| | - Fernando Q Cunha
- Department of Pharmacology, University of Sao Paulo, Ribeirao Preto, Brazil
| | - Gerard Karsenty
- Department of Genetics and Development, Columbia University, New York, NY, USA
| | - Jeremy A Squire
- Department of Genetics, University of Sao Paulo, Ribeirao Preto, Brazil.,Department of Pathology and Molecular Medicine, Queen's University, Kingston, Canada
| | - Sergio A Uyemura
- Department of Toxicology, Bromatology, and Clinical Analysis, University of Sao Paulo, Ribeirao Preto, Brazil
| | - Vinicius Kannen
- Department of Toxicology, Bromatology, and Clinical Analysis, University of Sao Paulo, Ribeirao Preto, Brazil
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Pocobelli G, Yu O, Ziebell RA, Aiello Bowles EJ, Fujii MM, Sterrett AT, Boggs JM, Chen L, Boudreau DM, Ritzwoller DP, Hubbard RA, Chubak J. Use of antidepressants after colon cancer diagnosis and risk of recurrence. Psychooncology 2019; 28:750-758. [PMID: 30703275 DOI: 10.1002/pon.5015] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2018] [Revised: 01/22/2019] [Accepted: 01/25/2019] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Prior research examining the association between use of antidepressants after colon cancer diagnosis and risk of recurrence is scant. We evaluated this association among colon cancer patients diagnosed at two integrated health care delivery systems in the United States. METHODS We conducted a cohort study of stage I to IIIA colon cancer patients diagnosed at greater than or equal to 18 years of age at Kaiser Permanente Colorado and Kaiser Permanente Washington during 1995 to 2014. We used pharmacy records to identify dispensings for antidepressants and tumor registry records and patients' medical charts to identify cancer recurrences. Using Cox proportional hazards models, we estimated the adjusted hazard ratio (HR) of colon cancer recurrence comparing patients who used antidepressants after diagnosis to those who did not. We also evaluated the risk associated with use of selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) separately. RESULTS Among the 1923 eligible colon cancer patients, 807 (42%) used an antidepressant after diagnosis and 139 had a colon cancer recurrence during an average 5.6 years of follow-up. Use of antidepressants after colon cancer diagnosis was not associated with risk of recurrence (HR: 1.14; 95% confidence interval [CI], 0.69-1.87). The HR for use of SSRIs was 1.22 (95% CI, 0.64-2.30), and for TCAs, it was 1.18 (95% CI, 0.68-2.07). CONCLUSIONS Our findings suggest that use of antidepressants after colon cancer diagnosis was common and not associated with risk of recurrence. Future larger studies with greater power to examine risk associated with individual antidepressants would be valuable additions to the evidence base.
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Affiliation(s)
- Gaia Pocobelli
- Kaiser Permanente Washington Health Research Institute, Seattle, Washington
| | - Onchee Yu
- Kaiser Permanente Washington Health Research Institute, Seattle, Washington
| | - Rebecca A Ziebell
- Kaiser Permanente Washington Health Research Institute, Seattle, Washington
| | | | - Monica M Fujii
- Kaiser Permanente Washington Health Research Institute, Seattle, Washington
| | - Andrew T Sterrett
- Kaiser Permanente Colorado Institute for Health Research, Denver, Colorado
| | - Jennifer M Boggs
- Kaiser Permanente Colorado Institute for Health Research, Denver, Colorado
| | - Lu Chen
- Kaiser Permanente Washington Health Research Institute, Seattle, Washington
| | - Denise M Boudreau
- Kaiser Permanente Washington Health Research Institute, Seattle, Washington.,Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington.,School of Pharmacy, University of Washington, Seattle, Washington
| | - Debra P Ritzwoller
- Kaiser Permanente Colorado Institute for Health Research, Denver, Colorado
| | - Rebecca A Hubbard
- Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Jessica Chubak
- Kaiser Permanente Washington Health Research Institute, Seattle, Washington.,Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington
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Abstract
During cancer progression, tumor cells interact with the neighboring environment, including neuronal tissue. The important influence of the nervous system on growth and metastasis of cancer is now widely accepted. As such, using medications that traditionally target the nervous system may be an avenue toward treating cancer. The focus of this review is to detail how several classes of medications, traditionally used to treat nervous system disorders, impact cancer. Specifically, we review the preclinical and clinical evidence that support the use of anti-β-adrenergic, anticholinergic, antipsychotic, and antidepressant medications to treat some cancers. In addition, we discuss the use of ablative modalities, such as physical and chemical denervation, to treat cancer or protect against cancer development. Using the medications that target the nervous system to treat cancer is a promising addition to an existing therapy or an alternative treatment strategy. Furthermore, rapidly expanding basic science research in this area will likely yield novel cancer therapies that work by targeting the nervous system.
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9
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Huang RY, Hsieh KP, Huang WW, Yang YH. Use of lithium and cancer risk in patients with bipolar disorder: population-based cohort study. Br J Psychiatry 2016; 209:393-399. [PMID: 27388574 DOI: 10.1192/bjp.bp.116.181362] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2015] [Accepted: 02/12/2016] [Indexed: 01/06/2023]
Abstract
BACKGROUND Lithium inhibits glycogen synthase kinase-3, which is an enzyme involved in the pathogenesis of cancer. AIMS To investigate the association between lithium and cancer risk in patients with bipolar disorder. METHOD A retrospective cohort study was designed using the National Health Insurance Research Database (NHIRD) in Taiwan. Patients using lithium comprised the index drug group and patients using anticonvulsants only comprised the control group. Time-dependent Cox regression was used to evaluate the hazard ratios (HRs) for risk of cancer. RESULTS Compared with anticonvulsant-only exposure, lithium exposure was associated with significantly lower cancer risk (HR = 0.735, 95% CI 0.554-0.974). The hazard ratios for the first, second and third tertiles of the cumulative defined daily dose were 0.762 (95% CI 0.516-1.125), 0.919 (95% CI 0.640-1.318) and 0.552 (95% CI 0.367-0.831), respectively. CONCLUSIONS Lithium is associated with reduced overall cancer risk in patients with bipolar disorder. A dose-response relationship for cancer risk reduction was observed.
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Affiliation(s)
- Ru-Yu Huang
- Ru-Yu Huang, MSc, School of Pharmacy, Master Program in Clinical Pharmacy, Kaohsiung Medical University, Kaohsiung; Kun-Pin Hsieh, PharmD, PhD, School of Pharmacy, College of Pharmacy, Kaohsiung Medical University and Department of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung; Wan-Wen Huang, MSc, School of Pharmacy, Master Program in Clinical Pharmacy, Kaohsiung Medical University, Kaohsiung; Yi-Hsin Yang, PhD, School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Kun-Pin Hsieh
- Ru-Yu Huang, MSc, School of Pharmacy, Master Program in Clinical Pharmacy, Kaohsiung Medical University, Kaohsiung; Kun-Pin Hsieh, PharmD, PhD, School of Pharmacy, College of Pharmacy, Kaohsiung Medical University and Department of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung; Wan-Wen Huang, MSc, School of Pharmacy, Master Program in Clinical Pharmacy, Kaohsiung Medical University, Kaohsiung; Yi-Hsin Yang, PhD, School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Wen Huang
- Ru-Yu Huang, MSc, School of Pharmacy, Master Program in Clinical Pharmacy, Kaohsiung Medical University, Kaohsiung; Kun-Pin Hsieh, PharmD, PhD, School of Pharmacy, College of Pharmacy, Kaohsiung Medical University and Department of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung; Wan-Wen Huang, MSc, School of Pharmacy, Master Program in Clinical Pharmacy, Kaohsiung Medical University, Kaohsiung; Yi-Hsin Yang, PhD, School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Hsin Yang
- Ru-Yu Huang, MSc, School of Pharmacy, Master Program in Clinical Pharmacy, Kaohsiung Medical University, Kaohsiung; Kun-Pin Hsieh, PharmD, PhD, School of Pharmacy, College of Pharmacy, Kaohsiung Medical University and Department of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung; Wan-Wen Huang, MSc, School of Pharmacy, Master Program in Clinical Pharmacy, Kaohsiung Medical University, Kaohsiung; Yi-Hsin Yang, PhD, School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
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Chung CM, Kuo TM, Chiang SL, Wang ZH, Hung CC, Lane HY, Liu CS, Ko YC. Antidepressants in association with reducing risk of oral cancer occurrence: a nationwide population-based cohort and nested case-control studies. Oncotarget 2016; 7:11687-11695. [PMID: 26840257 PMCID: PMC4905503 DOI: 10.18632/oncotarget.7049] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2015] [Accepted: 01/20/2016] [Indexed: 11/25/2022] Open
Abstract
OBJECTIVES Several studies suggested that antidepressant use may increase or decrease the risk of cancer occurrence, depending on specific cancer types. The possible carcinogenic effect of antidepressants has received substantial attention; however, evidence remains inconclusive. Here we investigated associations between the use of antidepressants and occurrences of oral cancer (OC). METHODS Two million samples were randomly collected from the National Health Insurance Research Database in Taiwan, which covers 98% of the total population (23 million). All patients from2000 to 2009 were followed up. We identified 5103 patients newly diagnosed with OC after antidepressants use in addition to 20,412 non-OC matched subjects and 95,452 unmatched non-OC subjects. RESULTS In nested case control analysis, factors associating with OC, including age [OR = 1.02; 95% confidence interval (CI) = 1.01-1.03) and male (OR = 5.30; 95% CI = 4.92-5.70) were independently associated with increased risk of OC. Based on the functions of antidepressants, antidepressants treatment medications were further classified to investigate risk of OC. Selective serotonin reuptake inhibitors (OR = 0.61; 95% CI = 0.53-0.70) and tricyclic antidepressants (OR = 0.57; 95% CI = 0.52-0.63) were associated with reduced risk of OC. The risk of developing OC among subjects taking antidepressants was less than 26% [hazard ratio (HR) =0.74; 95% CI = 0.68-0.81] in prospective cohort study. The effect of a cumulative duration and dose was a significantly reduced risk of OC. CONCLUSIONS The association between antidepressant use and decreasing OC risk were demonstrated by both prospective and nested case-control studies.
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Affiliation(s)
- Chia-Min Chung
- Environment-Omics-Disease Research Center, China Medical University Hospital, Taichung, Taiwan
- Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan
| | - Tzer-Min Kuo
- Environment-Omics-Disease Research Center, China Medical University Hospital, Taichung, Taiwan
| | - Shang-Lun Chiang
- Environment-Omics-Disease Research Center, China Medical University Hospital, Taichung, Taiwan
- Department of Health Risk Management, College of Public Health, China Medical University, Taichung, Taiwan
| | - Zhi-Hong Wang
- Environment-Omics-Disease Research Center, China Medical University Hospital, Taichung, Taiwan
| | - Chung-Chieh Hung
- Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan
- Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan
| | - Hsien-Yuan Lane
- Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan
- Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan
| | - Chiu-Shong Liu
- Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Ying-Chin Ko
- Environment-Omics-Disease Research Center, China Medical University Hospital, Taichung, Taiwan
- Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan
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11
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Anti-depressant therapy and cancer risk: a nested case-control study. Eur Neuropsychopharmacol 2015; 25:1147-57. [PMID: 25934397 DOI: 10.1016/j.euroneuro.2015.04.010] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2015] [Revised: 03/28/2015] [Accepted: 04/03/2015] [Indexed: 11/21/2022]
Abstract
UNLABELLED Previous studies demonstrated a possible association between anti-depressant therapy with selective serotonin reuptake inhibitors (SSRI) and tricyclic anti-depressants (TCA), several genetic and hormonal pathways and cancer risk, with inconsistent results. Exposure to serotonin-norepinephrine reuptake inhibitors (SNRI) was not studied extensively. We sought to evaluate the association between exposure to SSRIs, TCAs and SNRIs and the five most common solid tumors. We conducted nested case-control studies using a large UK population-representative database. Cases were those with any medical code for the specific malignancy. For every case, four controls matched on age, sex, practice site, and duration of follow-up before index date were selected using incidence-density sampling. Exposure of interest was SSRI, SNRI or TCA therapy before index date. Odds ratios (ORs) and 95% CIs were estimated for each anti-depressant class using conditional logistic-regression analysis, adjusted for potential confounders, such as obesity, smoking history and alcohol consumption. RESULTS 109,096 cancer patients and 426,402 matched controls were included. Current SSRI users with treatment initiation>one year before index date had modestly higher risk for lung and breast cancers with ORs of 1.27 (95% CI 1.16-1.38) and 1.12 (95% CI 1.06-1.18), respectively. Among current TCA users, there was a higher risk only for lung cancers with OR of 1.45 (95% CI 1.31-1.6). There was no statistically significant association between current SNRI therapy and cancer risk. DISCUSSION Treatment with SSRI and TCA might be associated with increased lung cancer risk. SSRI therapy might be associated with modest increase in breast cancer risk.
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12
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Warnke I, Nordt C, Moock J, Kawohl W, Rössler W. Antidepressants: relationship to the time to psychiatric readmission and probability of being in hospital in depressive patients. Front Public Health 2014; 2:40. [PMID: 24847477 PMCID: PMC4021117 DOI: 10.3389/fpubh.2014.00040] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2014] [Accepted: 04/23/2014] [Indexed: 01/15/2023] Open
Abstract
Introduction: Although antidepressants play a major role in the treatment of patients with depression, it is unclear which specific antidepressants are more efficacious than others. This study aims to analyze the relationship between several antidepressant substances and the time to readmission as well as the probability of being in hospital in a given week by using prescription data. Methods: The database was health-insurance claim data from the new Federal States in Germany. The analysis consisted of all patients with unipolar depression at their index admission in 2007 (N = 1803). Patients were followed up for 2 years after discharge from index hospitalization. Statistical analyses were conducted by discrete-time hazards models and general estimation equation models, accounting for various predictors. Results: Of all prescribed antidepressant substances, sertraline was related to an increased time to readmission by 37% and to a reduction in the probability of being in hospital in a given week by 40%. However, it was prescribed to only about 5% of the patients. Conclusion: In this study, only sertraline appeared to have clinical and economic advantages. It is remarkable that just a minority of patients received sertraline in our study, thus differing from the prescription pattern in the US.
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Affiliation(s)
- Ingeborg Warnke
- Competence Tandem, Innovation Incubator, Leuphana University Lüneburg , Lüneburg , Germany ; Department of Psychiatry, Psychotherapy and Psychosomatics, Center for Social Psychiatry, University Hospital of Psychiatry , Zurich , Switzerland
| | - Carlos Nordt
- Department of Psychiatry, Psychotherapy and Psychosomatics, Center for Social Psychiatry, University Hospital of Psychiatry , Zurich , Switzerland
| | - Jörn Moock
- Competence Tandem, Innovation Incubator, Leuphana University Lüneburg , Lüneburg , Germany
| | - Wolfram Kawohl
- Competence Tandem, Innovation Incubator, Leuphana University Lüneburg , Lüneburg , Germany ; Department of Psychiatry, Psychotherapy and Psychosomatics, Center for Social Psychiatry, University Hospital of Psychiatry , Zurich , Switzerland ; University of Zurich , Zurich , Switzerland
| | - Wulf Rössler
- Competence Tandem, Innovation Incubator, Leuphana University Lüneburg , Lüneburg , Germany ; University of Zurich , Zurich , Switzerland ; Laboratory of Neuroscience, LIM27, Faculty of Medicine, University of Sao Paulo , Sao Paulo , Brazil
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Stopper H, Garcia SB, Waaga-Gasser AM, Kannen V. Antidepressant fluoxetine and its potential against colon tumors. World J Gastrointest Oncol 2014; 6:11-21. [PMID: 24578784 PMCID: PMC3936192 DOI: 10.4251/wjgo.v6.i1.11] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2013] [Revised: 10/21/2013] [Accepted: 12/11/2013] [Indexed: 02/05/2023] Open
Abstract
Colon cancer is one of the most common tumors worldwide, with increasing incidence in developing countries. Patients treated with fluoxetine (FLX) have a reduced incidence of colon cancer, although there still remains great controversy about the nature of its effects. Here we explore the latest achievements related to FLX treatment and colon cancer. Moreover, we discuss new ideas about the mechanisms of the effects of FLX treatment in colon cancer. This leads to the hypothesis of FLX arresting colon tumor cells at the at G1 cell-cycle phase through a control of the tumor-related energy generation machinery. We believe that the potential of FLX to act against tumor metabolism warrants further investigation.
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Goubran HA, Burnouf T, Radosevic M, El-Ekiaby M. The platelet-cancer loop. Eur J Intern Med 2013; 24:393-400. [PMID: 23433737 DOI: 10.1016/j.ejim.2013.01.017] [Citation(s) in RCA: 134] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2012] [Revised: 01/17/2013] [Accepted: 01/22/2013] [Indexed: 12/21/2022]
Abstract
The relationship between cancer and thrombosis has been established since 1865 when Armand Trousseau described superficial thrombophlebitis as forewarning sign of occult visceral malignancy. Platelets are the primary hemostatic tool and play a primordial role in cancer-induced thrombosis. Tumor-induced numerical and functional platelet abnormalities have been described in conjunction to changes in coagulation. Such changes are reported even in the absence of clinically detectable thrombosis and correlate with tumor progression and metastasis. Reciprocally, platelets seem to interplay with the tumors and the immune system, both directly and indirectly favoring tumor progressions, tethering and distant spread. A number of growth factors supporting tumor growth, angiogenesis and metastasis are released from the platelets. A reciprocating loop of tumor-induced platelet activation/platelet-induced tumor growth and dissemination is initiated, acting as a thrombosis trigger/tumor amplifier. Recent studies have demonstrated that the use of anti-platelet agents can break this loop resulting in a reduction of short-term risk for incident cancer, cancer mortality and metastasis. The beneficial effect in reduction in cancer-induced thrombosis remains to be established. The current review aims at shedding the light on the intimate reciprocal cross-talk between platelets and cancer and on exploring the potential beneficial effect of anti-platelet agents in breaking the deadly loop of tumor amplification.
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Affiliation(s)
- Hadi A Goubran
- Saskatoon Cancer Centre and College of Medicine, University of Saskatchewan, Saskatoon, Canada.
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