Risk of prostate cancer in patients with schizophrenia

Abstract

Objectives

To examine the rate of prostate cancer in a cohort of schizophrenia in-patients in the PSA-era as compared to expected rates. There is conflicting evidence on the relative risk of prostate cancer in men with schizophrenia.

Methods

the study sample was comprised of schizophrenia patients who had been admitted to a tertiary care mental health center between 1990 and 2011. The data for the sample was cross-referenced with the National Cancer Registry. Analyses of Standardized Incidence Rates (SIR) for prostate cancer and for lung cancer (representing an organ system not sensitive to sex hormones) were performed.

Results

Of 4,326 schizophrenia patients included in the present study, 181 (4.2%) were diagnosed with cancer at any site. Only 10 of these patients were diagnosed with prostate cancer. This reflects a reduced risk; SIR of 0.56 (95% CI 0.27–1.03). In the same cohort, 33 schizophrenia patients were diagnosed with lung cancer presenting a SIR of 1.43 (95% CI 0.98–2.01) in this sample.

Conclusions

The present study suggests a reduced rate of prostate cancer in patients admitted for schizophrenia. There are several possible explanations for this finding including chronic state of hyperprolactinemia induced by antipsychotic drugs.

Introduction

Incidence of various malignancies may be different in patients with schizophrenia compared to general population rates. Several reports showed increased risk for cancer in general in schizophrenia patients [1]. These observations have been ascribed to patients with serious mental illness primarily due to increase exposure to known cancer risk factor – notably lifestyle causes such as smoking, alcohol abuse and obesity. However, genetics and growing exposure to antipsychotics may play a role [2], [3].

Antipsychotics are playing an important role in the treatment of several psychiatric disorders. In the USA, Canada and Europe their use has significantly increased over the past 20 years, even in periods following regulatory warnings [4], [5], [6]. While traditionally reserved for patients with schizophrenia and related disorders, 60% of prescriptions are now for off-label indications such as dementia, depression, and personality disorders [4], [5], [6].

Antipsychotics have been associated with several side effects including hyperprolactinemia [7], [8], [9], a hormonal abnormality that in men is associated with gynecomastia, sexual dysfunction, infertility and decreased bone mineral density [9]. There is concern that antipsychotics, via their sustained elevation of prolactin levels, may increase the risk of certain hormone-related cancers [10], [11], [12]. The majority of observational studies focused on the association between antipsychotics and breast cancer incidence, as there is evidence associating prolactin to mammary carcinogenesis [13], [14].

Prostate cancer is a malignancy that is very sensitive to sex-hormones level. Conflicting data exists for prostate cancer incidence in patients with schizophrenia and possible role of chronic hyperprolactinemia. Prior studies investigating all cancer types in patients with schizophrenia showed reduced prostate cancer incidence compared to expected rate [15]. Mostly, those studies used old patients' registries starting in the 1940s to the 1960s. Another large nested case-control study showed no difference in prostate cancer rate in schizophrenic patients [16]. Those studies may not represent the current population of schizophrenia patients since awareness, PSA screening and longevity increased substantially in the past 20 years.

There is some evidence to support prolactin involvement in prostate tumorigenesis in animal models. Implantation of prolactin secreting pituitary tumors in rats increases prostate weight and enhances atypical hyperplasia in the prostate [17]. In a study of prostate development and carcinogenesis in prolactin receptor knockout mice, the knockout mice had a 28% reduction of intraepithelial neoplasia induced by SV40T viral challenge and no prostate tumors, but controls had a prostate tumor incidence of 9% (wild type) and 19% (heterozygous) [18]. Probasin–prolactin transgenic mice that overexpress the rat prolactin gene specifically in the prostate, develop dramatic enlargement of the prostate with diminished apoptosis [19].

Few human studies on possible role of prolactin in prostate cancer have been conducted suggesting a role of prolactin in progression of the cancer to hormone independent state [20]. However, a prospective case-control study investigating plasma prolactin in 144 men with prostate cancer matched with 289 controls did not find any correlation [21].

There is clearly a need for larger scale population studies to examine whether the pre-clinical data translates to a higher risk of prostate cancer in men. Given the paucity of research in this area, it is a medical and public health priority, to determine whether schizophrenia patients and many others exposed to antipsychotics are at an increased risk of prostate cancer. Accordingly, the primary goal of this contemporary, PSA-era study is to evaluate the rate of prostate cancer in a large cohort of schizophrenia inpatients in Israel.