Diabetes, prostate cancer screening and risk of low- and high-grade prostate cancer: an 11year historical population follow-up study of more than 1 million men.

Rachel Dankner,Paolo Boffetta,Ran D Balicer,Moshe Hoshen,Alla Berlin,Liraz Olmer,Havi Murad,Lital Keinan-Boker,Laurence S Freedman,Barbara Silverman

doi:10.1007/s00125-016-3972-x

Abstract

Aims/hypothesisAn inverse association has consistently been shown between diabetes and prostate cancer incidence. We investigated whether lower prostate cancer incidence among men with diabetes is attributable to lower detection due to prostate cancer screening patterns.MethodsWe studied a population-based historical cohort of 1,034,074 Israeli men aged 21–90 years, without a previous history of cancer. The cohort was followed-up from 2002 to 2012, according to diabetes morbidity, for frequency of prostate-specific antigen (PSA) testing, mean PSA values and detection of prostate cancer, after adjustment for age, ethnic origin, socioeconomic status and PSA testing.ResultsIn January 2002, 74,756 men had prevalent diabetes. During the 11 year follow-up, 765,483 (74%) remained diabetes-free and 193,835 developed diabetes. Approximately 10% more PSA screening was performed in men with than without diabetes, but the rate of PSA positivity (>4 μg/l) was 20% lower in men with diabetes. PSA values were already significantly lower in men who developed diabetes than in those who did not, 3 years before diabetes diagnosis. Reduced prostate cancer risk was observed among men with incident diabetes only for low–moderate grade tumours (Gleason score 2–6: adjusted HR 0.83; 95% CI 0.77, 0.89). No association was observed for high-grade tumours (Gleason score 7–10: HR 0.99; 95% CI 0.88, 1.11).Conclusions/interpretationOur findings suggest that diabetes comorbidity is a factor to be considered in prostate cancer screening strategies, and specifically in the interpretation of PSA levels. Furthermore, our demonstration of reduced incidence of low–moderate grade but not high-grade prostate cancer tumours among men with diabetes supports the possibility that low PSA levels, rather than lower tumour risk, explains the observed reduced incidence of prostate cancer in men with diabetes.Trial registration:ClinicalTrials.gov NCT02072902

Highlights

Many studies have shown an inverse association between diabetes and prostate cancer incidence; recent publications include two large meta-analyses of case–control and cohort studies [1], the European Prospective Investigation into Cancer and Nutrition (EPIC) study [2], and nationwide studies from Sweden [3] and Australia [4]
We investigated whether the observed lower incidence of prostate cancer among men with diabetes may be a consequence of prostate cancer screening
Comparison of prostate-specific antigen (PSA) values between men with and without diabetes To compare mean PSA values between men with and without diabetes, before and after diagnosis, we examined for each year during 2002–2012, mean PSA values of men diagnosed with diabetes in 2008 and of those not diagnosed with diabetes by the end of 2008

Summary

Introduction

Many studies have shown an inverse association between diabetes and prostate cancer incidence; recent publications include two large meta-analyses of case–control and cohort studies [1], the European Prospective Investigation into Cancer and Nutrition (EPIC) study [2], and nationwide studies from Sweden [3] and Australia [4]. Studies in Chinese populations have shown positive associations between diabetes and prostate cancer [12]. A few investigations of the association between diabetes and prostate cancer have stratified by grade of prostate cancer. Two Japanese studies [13, 14], a Korean study [15], a Swedish study [16] and a US retrospective study [17] reported positive associations between diabetes and aggressive prostate cancer. A meta-analysis of these studies revealed an inverse association for both low-grade and high-grade cancer, which was stronger for the former [19]

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Conclusion