The risk of prostate cancer for men on aspirin, statin or antidiabetic medications
Introduction
Prostate cancer is a leading cause of cancer death for men in the Western world [1]. Its burden on society is substantial and the direct costs of prostate cancer care in Sweden are expected to double until 2020 [2]. PSA testing and ultrasound guided biopsies remain the cornerstone of prostate cancer diagnostics. Referral to prostate biopsy may depend on age, family history of prostate cancer, ethnicity, total and free PSA levels, previous biopsy results or other biomarker levels. Considerable effort has been expended to improve the prediction of biopsy outcomes and different risk calculators have been developed to aid decision-making [3], [4]. Better risk prediction tools are needed due to increasing diagnosis-related costs, biopsy-related morbidity, including a rising incidence of infectious complications due to antibiotic-resistant bacteria [5], and increased costs and morbidity due to over-diagnosis and over-treatment [6].
A number of observational studies have addressed how statins, aspirin and metformin treatment affects the risk of prostate cancer. It has been suggested that prostate cancer risk is reduced by 10% in regular aspirin users [7]. This was supported by a meta-analysis in 2014 including 39 observational studies suggesting a risk reduction for prostate cancer (odds ratio (OR) 0.92), advanced prostate cancer (OR = 0.81) and prostate cancer mortality (OR = 0.86) [8]. This has also been found in randomised trials of aspirin versus placebo [9].
Statins have been suggested to be associated with a decreased incidence of several cancers including prostate cancer, possibly with a larger effect of the hydrophobic compared with the hydrophilic statins [10], [11], [12], [13]. Results are, however, conflicting and recent studies of men in the Prostate Cancer Prevention Trial (PCPT) and Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study showed no protective effect of statins with seven and four year follow-up, respectively [14], [15].
Moreover, antidiabetic drugs, particularly metformin, have been suggested to increase disease-specific survival after prostate cancer diagnosis, but evidence has been conflicting for the association between metformin treatment and prostate cancer risk [16], [17], [18].
The published observational studies have commonly lacked data on socioeconomic status, comorbidity or PSA levels. We incorporated such data from a large population-based cohort of men to assess whether aspirin, statins and antidiabetic medications were predictors of cancer risk following a prostate biopsy.
Section snippets
Study population
The study population for this retrospective cohort study were men in Stockholm County undergoing a PSA test between 2003 and 2012. For an analysis of the effect of different medications on PSA levels, we restricted the cohort to men undergoing a first PSA test between 2007 and 2012, providing at least four years from the start of the cohort and 2 years from the start of the Swedish Prescribed Drug Register in 2005. For an analysis of the effect of medications on the risk of prostate cancer
Results
For the period 2007–2012, 185,657 men without a prior prostate cancer or prostate biopsy had their first PSA test taken in Stockholm County. The prevalence of low-dose aspirin, statins and antidiabetic use was 12%, 12% and 4%, respectively, with a high degree of overlap between medications (see Table 1A). Men taking one or more of these medications tended to be older (mean age 65 versus 56; p < 0.001) and had significantly more comorbidities (p < 0.001).
For the same period, 18,574 men had their
Discussion
In this large, population-based cohort study, use of aspirin or statins were associated with lower PSA levels, and PSA was also substantially lower among men taking insulin or metformin compared with non-users. Use of these medications was not associated with a lower incidence of prostate cancer.
In line with previous knowledge, we report a slightly lower PSA among men on aspirin and statins, possibly affecting the results of previous observational studies without access to PSA data. More
Funding
The funding source had no role in the study design; collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. The researchers were all independent from the funding source.
Karolinska University Laboratory, Aleris Medilab, Unilabs and the Regional Prostate Cancer Registry for performing analyses and help to retrieve data. Carin Cavalli–Björkman and Britt-Marie Hune for their enthusiastic work as research nurses.
Conflict of interest statement
None declared.
Acknowledgements
This study was supported by grants from The Strategic Research Programme on Cancer (StratCan), Karolinska Institutet; the Linné Centre for Breast and Prostate Cancer (CRISP, number 70867901), Karolinska Institutet; The Swedish Research Council (number K2010-70X-20430-04-3) and The Swedish Cancer Society (numbers 11-0287, 11-0624 and 12-0765); Stiftelsen Johanna Hagstrand och Sigfrid Linnérs minne; Swedish Council for Working Life and Social Research (FAS), number 2012-0073; and the Swedish
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