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      Hydroxychloroquine and risk of development of cancers: a nationwide population-based cohort study

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          Abstract

          Background

          Hydroxychloroquine (HCQ), one of the disease-modifying antirheumatic drugs, may lead to an inhibition of autophagy. Autophagy, an intracellular self-defense mechanism for the lysosomal degradation of cytoplasmic components such as damaged organelles, plays a role in protecting against neoplasm growth but is also vital for cancer cells due to an increased intracellular metabolic waste.

          Methods

          Taiwan National Health Insurance Database was subjected to analysis to investigate the effect of HCQ exposure on cancer risk in patients with autoimmune diseases. Cancer incidence between patients with or without at least 12-month HCQ use was compared by propensity score-matched landmark analysis. A total of 100,000 participants were enrolled, including 7,662 patients who were diagnosed with autoimmune diseases between January 1, 2000, and December 31, 2012.

          Results

          After propensity score matching, HCQ user and nonuser groups consist of 1,933 patients with a mean follow-up time of 7.82 and 6.7 years, respectively. During the follow-up period, 93 HCQ users and 77 HCQ nonusers developed cancers. Meanwhile, Kaplan–Meier estimates showed no difference in the overall incidence of cancer between HCQ users and nonusers.

          Conclusion

          This propensity score-matched study of Taiwanese patients with autoimmune diseases suggested that HCQ exposure did not increase the cancer risk.

          Most cited references8

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          The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy.

          Hydroxychloroquine sulfate is widely used for the long-term treatment of autoimmune conditions but can cause irreversible toxic retinopathy. Prior estimations of risk were low but were based largely on short-term users or severe retinal toxicity (bull's eye maculopathy). The risk may be much higher because retinopathy can be detected earlier when using more sensitive screening techniques.
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            Chloroquine and hydroxychloroquine for cancer therapy

            Macroautophagy (herein referred to as autophagy) is a highly conserved mechanism for the lysosomal degradation of cytoplasmic components. Autophagy is critical for the maintenance of intracellular homeostasis, both in baseline conditions and in the context of adaptive responses to stress. In line with this notion, defects in the autophagic machinery have been etiologically associated with various human disorders including infectious, inflammatory and neoplastic conditions. Once tumors are established, however, autophagy sustains the survival of malignant cells, hence representing an appealing target for the design of novel anticancer regimens. Accordingly, inhibitors of autophagy including chloroquine and hydroxychloroquine have been shown to mediate substantial antineoplastic effects in preclinical models, especially when combined with chemo- or radiotherapeutic interventions. The pharmacological profile of chloroquine and hydroxychloroquine, however, appear to involve mechanisms other than autophagy inhibition. Here, we discuss the dual role of autophagy in oncogenesis and tumor progression, and summarize the results or design of clinical studies recently completed or initiated to evaluate the therapeutic activity of chloroquine derivatives in cancer patients.
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              Cancer and autoimmune diseases.

              The association between autoimmunity and cancer is well established. Cancer has been implicated in some autoimmune disorders (AID), such as scleroderma and myositis. On the other hand, many autoimmune disorders and immunosuppressive therapy, have been linked to an increased risk for cancer. We reviewed the accumulating data on the association between autoimmunity and cancer during the past three years, with an emphasis on large cohorts, as well as concept changing discoveries in the association of cancer and auto-immunity.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                2018
                20 August 2018
                : 14
                : 1435-1443
                Affiliations
                [1 ]Division of Critical Care, Departmen of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
                [2 ]Division of Hematology and Oncology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
                [3 ]Division of Nephrology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan, chiachu@ 123456cch.org.tw
                [4 ]Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
                [5 ]Internal Medicine Research Center, Changhua Christian Hospital, Changhua, Taiwan, 179297@ 123456cch.org.tw
                [6 ]Graduate Institute of Statistics and Information Science, National Changhua University of Education, Changhua, Taiwan, 179297@ 123456cch.org.tw
                [7 ]Department of Internal Medicine, Kuang Tien General Hospital, Taichung, Taiwan, chiachu@ 123456cch.org.tw
                [8 ]School of Medicine, Chung-Shan Medical University, Taichung, Taiwan, chiachu@ 123456cch.org.tw
                [9 ]Department of Nutrition, Hungkuang University, Taichung, Taiwan, chiachu@ 123456cch.org.tw
                Author notes
                Correspondence: Chia-Chu Chang, Division of Nephrology, Department of Internal Medicine, Changhua Christian Hospital, 135 Nanhsiao St, Changhua 500, Taiwan, Tel +886 4 723 8595 ext 1031, Fax +886 4 722 8289, Email chiachu@ 123456cch.org.tw
                Chew-Teng Kor, Internal Medicine Research Center, Changhua Christian Hospital, 135 Nanhsiao Street, Changhua 500, Taiwan, Tel +886 4 723 8595 ext 4738, Fax +886 2 2826 4049, Email 179297@ 123456cch.org.tw
                Article
                tcrm-14-1435
                10.2147/TCRM.S175581
                6108344
                072c8e00-bc9a-4c18-b991-23229dc87414
                © 2018 Mao et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Categories
                Original Research

                Medicine
                hydroxychloroquine,autophagy,cancer,autoimmune diseases,propensity score
                Medicine
                hydroxychloroquine, autophagy, cancer, autoimmune diseases, propensity score

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