title: Diabetes, prostate cancer screening and risk of low- and high-grade prostate cancer: an 11 year historical population follow-up study of more than 1 million men.
abstract: An 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.
  
  
  
  We 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.
  
  
  
  In 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).
  
  
  
  Our 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.
  
  
  
  ClinicalTrials.gov NCT02072902.
authors.affiliation: Unit for Cardiovascular Epidemiology, The Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Tel Hashomer, 52621, Israel. racheld@gertner.health.gov.il.|Sackler Faculty of Medicine, School of Public Health, Department of Epidemiology and Preventive Medicine, Tel Aviv University, Tel Aviv, Israel. racheld@gertner.health.gov.il.|Patient Oriented Research, The Feinstein Institute for Medical Research, Manhasset, NY, USA. racheld@gertner.health.gov.il.
authors.forename: Rachel
authors.initials: R
authors.lastname: Dankner
authors.affiliation: Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Paolo
authors.initials: P
authors.lastname: Boffetta
authors.affiliation: Israel Center for Disease Control (ICDC), Israel Ministry of Health, Tel Hashomer, Israel.|School of Public Health, Faculty of Social Welfare and Health Sciences, Haifa University, Haifa, Israel.
authors.forename: Lital
authors.initials: L
authors.lastname: Keinan-Boker
authors.affiliation: Clalit Research Institute, Clalit Health Services, Tel Aviv, Israel.|Public Health Department, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Ran D
authors.initials: RD
authors.lastname: Balicer
authors.affiliation: Unit for Cardiovascular Epidemiology, The Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Tel Hashomer, 52621, Israel.|Clalit Research Institute, Clalit Health Services, Tel Aviv, Israel.
authors.forename: Alla
authors.initials: A
authors.lastname: Berlin
authors.affiliation: Biostatistics Unit, Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Liraz
authors.initials: L
authors.lastname: Olmer
authors.affiliation: Biostatistics Unit, Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Havi
authors.initials: H
authors.lastname: Murad
authors.affiliation: Sackler Faculty of Medicine, School of Public Health, Department of Epidemiology and Preventive Medicine, Tel Aviv University, Tel Aviv, Israel.|Israel Center for Disease Control (ICDC), Israel Ministry of Health, Tel Hashomer, Israel.
authors.forename: Barbara
authors.initials: B
authors.lastname: Silverman
authors.affiliation: Clalit Research Institute, Clalit Health Services, Tel Aviv, Israel.
authors.forename: Moshe
authors.initials: M
authors.lastname: Hoshen
authors.affiliation: Sackler Faculty of Medicine, School of Public Health, Department of Epidemiology and Preventive Medicine, Tel Aviv University, Tel Aviv, Israel.|Biostatistics Unit, Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Laurence S
authors.initials: LS
authors.lastname: Freedman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology*; D055088:Early Detection of Cancer; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology*; D012923:Social Class; D055815:Young Adult
chemical_list: D017430:Prostate-Specific Antigen
keywords: Diabetes; Ethnic origin; Gleason score; PSA screening; PSA testing; Prostate cancer; Socioeconomic status