Risk for cancer in a cohort of patients hospitalized for schizophrenia in Denmark, 1969–1993

Dalton, Susanne Oksbjerg; Mellemkjær, Lene; Thomassen, Lars; Mortensen, Preben Bo; Johansen, Christoffer

doi:10.1016/j.schres.2004.11.009

Cited by 124 publications

(133 citation statements)

References 25 publications

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“…Although there was no clear trend by number of prescriptions or length of follow-up, risk was further reduced among long-term users with more than 10 prescriptions. Studies of patients with schizophrenia in Denmark and Finland have reported reduced risks for rectal cancer but not for colon cancer (Mortensen, 1989;Gulbinat et al, 1992;Mortensen, 1994;Lichtermann et al, 2001;Dalton et al, 2005) whereas we additionally observed a reduced incidence of colon cancer among female users of neuroleptic medication in the present study. Established risk factors for rectal and colon cancer are similar and we would expect exposure to mutual risk factors, such as high intake of alcohol, little exercise and high intake of meat or low intake of vegetables (Potter, 1999), to be more frequent among our cohort of neuroleptic users.…”

Section: Discussionsupporting

confidence: 54%

“…In schizophrenia, the hypothesis of a lowered host susceptibility to cancer in general has been raised (Catts and Catts, 2000) but the present study indicated that the reduced risk for rectal cancer was not confined to patients with schizophrenia. Prostate cancer was of a priori interest given the reduced risk reported in patients with schizophrenia (Mortensen, 1989;Mortensen, 1994;Lichtermann et al, 2001;Dalton et al, 2005) and the finding of a reduced risk among men with schizophrenia treated with high-dose phenothiazines (IRR, 0.33; 95% CI, 0.12 -0.94) in a small Danish case -control study (Mortensen, 1992). Although in the present study there was no clear trend by number of prescriptions or length of follow-up we did find a 44% lower risk among long-term users with multiple prescriptions.…”

Section: Discussionmentioning

confidence: 99%

“…Neuroleptics have been hypothesised to account for the reduced cancer occurrence observed in patients with schizophrenia in a number of studies (Dupont et al, 1986;Mortensen, 1989;Gulbinat et al, 1992;Mortensen, 1994;Lichtermann et al, 2001;Dalton et al, 2005). This reduction has been found primarily in men in smoking-related cancers, and in prostate and rectal cancer.…”

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confidence: 99%

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Cancer risk among users of neuroleptic medication: a population-based cohort study

et al. 2006

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It has been suggested that neuroleptic medication may decrease cancer risk. We compared cancer risks in a population-based cohort study of 25 264 users (X2 prescriptions) of neuroleptic medications in the county of North Jutland, Denmark, during 1989Denmark, during -2002, with that of county residents who did not receive such prescriptions. Statistical analyses were based on age-standardisation and Poisson regression analysis, adjusting for age, calendar period, COPD, liver cirrhosis or alcoholism, use of NSAID, and, for breast cancer, additionally for use of hormone therapy, age at first birth, and number of children. Use of neuroleptic medications was associated with a decreased risk for rectal cancer in both women and men (adjusted IRRs of 0.61 (95% confidence interval, 0.41 -0.91) and 0.82 (0.56 -1.19), respectively) and for colon cancer in female users (0.78; 0.62 -0.98). Some risk reduction was seen for prostate cancer (0.87; 0.69 -1.08), but breast cancer risk was close to unity (0.93; 0.74 -1.17). Overall, treatment with neuroleptic medications was not related to a reduced risk of cancer, but for cancers of the rectum, colon and prostate there were suggestive decreases in risk.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Cancer risk among users of neuroleptic medication: a population-based cohort study

et al. 2006

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“…Patients with schizophrenia who receive DR antagonists have a reduced incidence of cancer of the rectum, colon, prostate and uterine cervix (2,3). Patients with Parkinson's disease, which functionally similar to disease-induced DR antagonism, also have a lower incidence of cancer.…”

Section: Introductionmentioning

confidence: 99%

DR2 blocker thioridazine: A promising drug for ovarian cancer therapy

Yong

Tian

et al. 2017

Oncol Lett

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Abstract. Dopamine receptor 2 (DR2) may be a biomarker for various types of cancer. Ovarian cancer cells overexpress DR2; therefore, blocking DR2 may be a novel treatment strategy for ovarian cancer. Thioridazine, a DR2 blocker, has antineoplastic activity in a variety of cancer cells. In view of the requirement for novel therapeutic agents in ovarian cancer, the present study aimed to determine the potential effects of thioridazine in vitro and in vivo. It was revealed that the DR2 blocker thioridazine induced cell death in a dose-dependent manner in ovarian cancer cells. Thioridazine treatment induced apoptosis and autophagy, which may be attributed to an increased level of reactive oxygen species and associated DNA damage. Additionally, the expression of various proteins increased with oxidative stress, including nuclear factor E2-related factor 2, which is a pivotal transcriptional factor involved in cellular responses to oxidative stress. Heme oxygenase 1, NAPDH quinone dehydrogenase 1 and hypoxia inducible factor-1α and phosphorylated (p)-protein kinase B expression was significantly decreased, and the expression level of p-extracellular signal-related kinases and p-P38 was increased. Using 3-methyl adenine to inhibit autophagy caused the rate of apoptosis to increase. Thioridazine inhibited the growth of SKOV3 xenografts in nude mice. The present study demonstrated that the DR2 blocker thioridazine exhibited anticancer effects in vitro and in vivo, suggesting that thioridazine may be used as a potential drug in ovarian cancer therapy. IntroductionEpithelial ovarian cancer is the leading cause of mortality among gynecological types of cancer. Surgical debulking combined with chemotherapy is the standard therapeutic strategy. However, the relapse rate is high, primarily due to the development of chemotherapy resistance (1), therefore, novel modalities must be explored.Dopamine receptor (DR) expression may be associated with the development of various types of cancer. Patients with schizophrenia who receive DR antagonists have a reduced incidence of cancer of the rectum, colon, prostate and uterine cervix (2,3). Patients with Parkinson's disease, which functionally similar to disease-induced DR antagonism, also have a lower incidence of cancer. It was hypothesized that DR may be a biomarker for cancer (4). Knockdown/blocking of DR2 inhibited the proliferation of cancer cells, including cancer stem cells (5). This suggested that DR2 may be a treatment target for types of cancer that expresses dopamine receptor 2.Thioridazine is a DR2 antagonist and has been clinically approved to treat schizophrenia and other psychotic disorders (6). Of note, thioridazine exhibits anticancer action in breast cancer, leukemia, hepatoma and cervical carcinoma (5,7-9). Ovarian cancer cells express a number of DRs, with the exception of DR3 (10), suggesting that thioridazine may be used to treat ovarian cancer. In the present study, the effects of thioridazine on ovarian cancer were explored in vitro and in vivo. The findings sug...

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“…These data contrast with previous data that tend to report no difference. 8,30,35 However, the age of the Goldacre et al 8 cohort was young in terms of cancer incidence, with a modal age group of 25 to 29 years and an average follow-up period of 12.6 years. The Catts meta-analysis that subsequently included 4 studies found a reduced risk of colon cancer (SIR 0.84; 95% CI 0.70 to 1.00).…”

Section: Incidence At Other Cancer Sitesmentioning

confidence: 99%

Schizophrenia and Cancer: In 2010 Do We Understand the Connection?

Bushe

Hodgson²

2010

Can J Psychiatry

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In recent years, there has been a plethora of cancer mortality and incidence data reported in schizophrenia. Despite this, there has been little focus on cancer in schizophrenia guidelines. Additionally, there have been suggestions that schizophrenia may provide inherent protection against cancer. The goal of this review is to establish, using recent data, the incidence and mortality rates for cancer in schizophrenia. Method: We identified systematic reviews and meta-analyses and undertook a search using the Medical Subject Headings' entry terms schizophrenia and neoplasm. Results: Incidence and mortality rates for cancer in schizophrenia are increased, compared with relevant general populations. Data are not uniformly reported and cohort ages tend to be young for expected cancer incidence. Despite the young cohort ages, the incidence of the major cancers-lung and breast-are substantially increased. Confounders are often not measured in the epidemiologic databases. When lung cancer is adjusted for smoking rates, there appears to be a lower risk of lung cancer than expected providing some basis to support an inherently reduced risk of cancer. There may also be a dissonance between incidence and mortality rates that suggest a prejudice against either diagnosis or treatment of these vulnerable patients. Conclusion: A single definitive study of schizophrenia and cancer is unfeasible, and future research will lean heavily on systematic review and meta-analysis. Researchers should report cancer data to include age and follow-up data and cohort overlap. Cancer accounts for almost an equivalent mortality as cardiovascular disease.

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Risk for cancer in a cohort of patients hospitalized for schizophrenia in Denmark, 1969–1993

Cited by 124 publications

References 25 publications

Cancer risk among users of neuroleptic medication: a population-based cohort study

Cancer risk among users of neuroleptic medication: a population-based cohort study

DR2 blocker thioridazine: A promising drug for ovarian cancer therapy

Schizophrenia and Cancer: In 2010 Do We Understand the Connection?

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