Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N=4532)

被引:388
作者
Montopoli, M. [1 ,2 ]
Zumerle, S. [2 ,3 ]
Vettor, R. [3 ]
Rugge, M. [3 ,4 ]
Zorzi, M. [4 ]
Catapano, C., V [5 ]
Carbone, G. M. [5 ]
Cavalli, A. [6 ]
Pagano, F. [2 ]
Ragazzi, E. [1 ]
Prayer-Galetti, T. [7 ]
Alimonti, A. [2 ,3 ,5 ,8 ]
机构
[1] Univ Padua, Dept Pharmaceut & Pharmacol Sci, Padua, Italy
[2] Fdn Ric Biomed Avanzata, VIMM Veneto Inst Mol Med, Padua, Italy
[3] Univ Padua, Dept Med, Padua, Italy
[4] Veneto Tumour Registry Azienda Zero, Padua, Italy
[5] Univ Svizzera Italiana, Inst Oncol Res, Oncol Inst Southern Switzerland, Bellinzona, Switzerland
[6] Univ Svizzera Italiana, Inst Res Biomed, Bellinzona, Switzerland
[7] Azienda Osped Padova, Dept Oncol & Gastroenterol Sci, Urol Unit, Padua, Italy
[8] Swiss Fed Inst Technol, Dept Hlth Sci & Technol, Zurich, Switzerland
基金
欧洲研究理事会; 瑞士国家科学基金会;
关键词
androgen-deprivation therapy; COVID-19; prostate cancer; POTENTIAL TARGET; PROTEASE TMPRSS2; CORONAVIRUS; VIRUS;
D O I
10.1016/j.annonc.2020.04.479
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Cell entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) depends on binding of the viral spike (S) proteins to angiotensin-converting enzyme 2 and on S protein priming by TMPRSS2. Inhibition of TMPRSS2 may work to block or decrease the severity of SARS-CoV-2 infections. Intriguingly, TMPRSS2 is an androgen-regulated gene that is up-regulated in prostate cancer where it supports tumor progression and is involved in a frequent genetic translocation with the ERG gene. First-or second-generation androgen-deprivation therapies (ADTs) decrease the levels of TMPRSS2. Here we put forward the hypothesis that ADTs may protect patients affected by prostate cancer from SARS-CoV-2 infections. Materials and methods: We extracted data regarding 9280 patients (4532 males) with laboratory-confirmed SARS-CoV2 infection from 68 hospitals in Veneto, one of the Italian regions that was most affected by the coronavirus disease 2019 (COVID-19) pandemic. The parameters used for each COVID-19-positive patient were sex, hospitalization, admission to intensive care unit, death, tumor diagnosis, prostate cancer diagnosis, and ADT. Results: There were evaluable 9280 SARS-CoV-2-positive patients in Veneto on 1 April 2020. Overall, males developed more severe complications, were more frequently hospitalized, and had a worse clinical outcome than females. Considering only the Veneto male population (2.4 million men), 0.2% and 0.3% of non-cancer and cancer patients, respectively, tested positive for SARS-CoV-2. Comparing the total number of SARS-CoV-2-positive cases, prostate cancer patients receiving ADT had a significantly lower risk of SARS-CoV-2 infection compared with patients who did not receive ADT (OR 4.05;95% CI 1.55-10.59). A greater difference was found comparing prostate cancer patients receiving ADT with patients with any other type of cancer (OR 4.86; 95% CI 1.88-12.56). Conclusion: Our data suggest that cancer patients have an increased risk of SARS-CoV-2 infections compared with noncancer patients. However, prostate cancer patients receiving ADT appear to be partially protected from SARS-CoV-2 infections.
引用
收藏
页码:1040 / 1045
页数:6
相关论文
共 40 条
[1]   Glucocorticoid Receptor Confers Resistance to Antiandrogens by Bypassing Androgen Receptor Blockade [J].
Arora, Vivek K. ;
Schenkein, Emily ;
Murali, Rajmohan ;
Subudhi, Sumit K. ;
Wongvipat, John ;
Balbas, Minna D. ;
Shah, Neel ;
Cai, Ling ;
Efstathiou, Eleni ;
Logothetis, Chris ;
Zheng, Deyou ;
Sawyers, Charles L. .
CELL, 2013, 155 (06) :1309-1322
[2]   Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer [J].
Asangani, Irfan A. ;
Dommeti, Vijaya L. ;
Wang, Xiaoju ;
Malik, Rohit ;
Cieslik, Marcin ;
Yang, Rendong ;
Escara-Wilke, June ;
Wilder-Romans, Kari ;
Dhanireddy, Sudheer ;
Engelke, Carl ;
Iyer, Mathew K. ;
Jing, Xiaojun ;
Wu, Yi-Mi ;
Cao, Xuhong ;
Qin, Zhaohui S. ;
Wang, Shaomeng ;
Feng, Felix Y. ;
Chinnaiyan, Arul M. .
NATURE, 2014, 510 (7504) :278-+
[3]   Targeting potential drivers of COVID-19: Neutrophil extracellular traps [J].
Barnes, Betsy J. ;
Adrover, Jose M. ;
Baxter-Stoltzfus, Amelia ;
Borczuk, Alain ;
Cools-Lartigue, Jonathan ;
Crawford, James M. ;
Dassler-Plenker, Juliane ;
Guerci, Philippe ;
Huynh, Caroline ;
Knight, Jason S. ;
Loda, Massimo ;
Looney, Mark R. ;
McAllister, Florencia ;
Rayes, Roni ;
Renaud, Stephane ;
Rousseau, Simon ;
Salvatore, Steven ;
Schwartz, Robert E. ;
Spicer, Jonathan D. ;
Yost, Christian C. ;
Weber, Andrew ;
Zuo, Yu ;
Egeblad, Mikala .
JOURNAL OF EXPERIMENTAL MEDICINE, 2020, 217 (06)
[4]   Type II Transmembrane Serine Proteases [J].
Bugge, Thomas H. ;
Antalis, Toni M. ;
Wu, Qingyu .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (35) :23177-23181
[5]   Sex difference and smoking predisposition in patients with COVID-19 [J].
Cai, Hua .
LANCET RESPIRATORY MEDICINE, 2020, 8 (04) :E20-E20
[6]   Type II transmembrane serine proteases in cancer and viral infections [J].
Choi, So-Young ;
Bertram, Stephanie ;
Glowacka, Ilona ;
Park, Young Woo ;
Poehlmann, Stefan .
TRENDS IN MOLECULAR MEDICINE, 2009, 15 (07) :303-312
[7]   Identification of a novel coronavirus in patients with severe acute respiratory syndrome [J].
Drosten, C ;
Günther, S ;
Preiser, W ;
van der Werf, S ;
Brodt, HR ;
Becker, S ;
Rabenau, H ;
Panning, M ;
Kolesnikova, L ;
Fouchier, RAM ;
Berger, A ;
Burguière, AM ;
Cinatl, J ;
Eickmann, M ;
Escriou, N ;
Grywna, K ;
Kramme, S ;
Manuguerra, JC ;
Müller, S ;
Rickerts, V ;
Stürmer, M ;
Vieth, S ;
Klenk, HD ;
Osterhaus, ADME ;
Schmitz, H ;
Doerr, HW .
NEW ENGLAND JOURNAL OF MEDICINE, 2003, 348 (20) :1967-1976
[8]   Exploitation of Castration-Resistant Prostate Cancer Transcription Factor Dependencies by the Novel BET Inhibitor ABBV-075 [J].
Faivre, Emily J. ;
Wilcox, Denise ;
Lin, Xiaoyu ;
Hessler, Paul ;
Torrent, Maricel ;
He, Wei ;
Uziel, Tamar ;
Albert, Daniel H. ;
McDaniel, Keith ;
Kati, Warren ;
Shen, Yu .
MOLECULAR CANCER RESEARCH, 2017, 15 (01) :35-44
[9]   Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018 [J].
Ferlay, J. ;
Colombet, M. ;
Soerjomataram, I. ;
Dyba, T. ;
Randi, G. ;
Bettio, M. ;
Gavin, A. ;
Visser, O. ;
Bray, F. .
EUROPEAN JOURNAL OF CANCER, 2018, 103 :356-387
[10]   Evidence that TMPRSS2 Activates the Severe Acute Respiratory Syndrome Coronavirus Spike Protein for Membrane Fusion and Reduces Viral Control by the Humoral Immune Response [J].
Glowacka, Ilona ;
Bertram, Stephanie ;
Mueller, Marcel A. ;
Allen, Paul ;
Soilleux, Elizabeth ;
Pfefferle, Susanne ;
Steffen, Imke ;
Tsegaye, Theodros Solomon ;
He, Yuxian ;
Gnirss, Kerstin ;
Niemeyer, Daniela ;
Schneider, Heike ;
Drosten, Christian ;
Poehlmann, Stefan .
JOURNAL OF VIROLOGY, 2011, 85 (09) :4122-4134