Diabetes and prostate cancer risk in the REDUCE trial (original) (raw)

Diabetes and Risk of Prostate Cancer in a Prospective Cohort of US Men

One previous study has suggested that diabetes may decrease risk of prostate cancer but only several years after diagnosis of diabetes. The authors examined the role of timing of diabetes diagnosis in relation to risk of prostate cancer among men in the Cancer Prevention Study II Nutrition Cohort. Participants in the study completed a mailed questionnaire including information on diabetes at enrollment in 1992 and at follow-up questionnaires in 1997 and 1999. Historical information on diabetes was also available from a previous study in 1982. The authors documented 5,318 cases of incident prostate cancer through August 31, 2001, among 72,670 men. Results from Cox proportional hazards models showed that diabetes was associated with a lower incidence of prostate cancer (rate ratio (RR) = 0.67, 95% confidence interval (CI): 0.60, 0.75). This association differed significantly by time since diagnosis of diabetes (p < 0.0002); risk of prostate cancer was slightly increased during the first 3 years after diagnosis of diabetes (RR = 1.23, 95% CI: 0.92, 1.65) but was reduced among men diagnosed 4 or more years before (RR = 0.63, 95% CI: 0.56, 0.71). Study results are consistent with the hypothesis that diabetes is associated with reduced risk of prostate cancer but only several years after diagnosis of diabetes. cohort studies; diabetes mellitus; prostatic neoplasms Abbreviations: CI, confidence interval; CPS, Cancer Prevention Study; RR, rate ratio.

Association between metabolic syndrome, diabetes mellitus and prostate cancer risk

Prostate Cancer and Prostatic Diseases, 2013

BACKGROUND: The worldwide incidence of diabetes mellitus is rapidly increasing. There is recent interest in the influence of glucose metabolism on oncogenesis. We investigated the role of diabetes mellitus and the metabolic syndrome (MS) on prostate cancer development. METHODS: This study consisted of 11 541 men with coronary heart disease screened to participate in a secondary cardiac prevention trial. MS was defined according to modified NCEP/ATP III criteria. Multivariable regression analysis accounting for competing risks was performed using a modified Cox proportional hazard model in order to assess the association between diabetes, the MS and the subsequent development of prostate cancer. RESULTS: At baseline, subjects were classified into one of the four groups: (1) 6119 (53%) with neither diabetic mellitus nor MS, (2) 3376 (29%) with the MS but without diabetes, (3) 560 (5%) with diabetes mellitus but without MS and (4) 1486 (13%) with both conditions. Median follow-up was 12.7 years (range 0-15.7 years). During follow-up, 459 new cases of prostate cancer were recorded. The age-adjusted hazard ratio (HR) for prostate cancer was reduced in diabetic patients compared with those without diabetes, 0.54 and 95% confidence interval of 0.40-0.73. No significant association was noted between the presence of MS and prostate cancer development. On multivariate analysis, diabetes mellitus continued to protect against the development of prostate cancer, this was more pronounced in the absence of MS (HR ¼ 0.43, P ¼ 0.01 for diabetes in the absence of MS; HR ¼ 0.64, P ¼ 0.08 in the presence of MS). CONCLUSIONS: The results of this study indicate an inverse association between type 2 diabetes mellitus and prostate cancer risk.

Effect of Diabetes Mellitus on High-grade Prostate Cancer Detection Among Japanese Obese Patients With Prostate-specific Antigen Less Than 10 ng/mL

Urology, 2012

OBJECTIVE To investigate the association of diabetes mellitus (DM) with prostate cancer (PCa) risk and grade among Japanese patients undergoing extended biopsy and to investigate how obesity modifies these relationships. METHODS We retrospectively evaluated the data from 2038 patients with a prostate-specific antigen (PSA) level Ͻ10 ng/mL undergoing initial extended biopsy at our institutions. The DM history was determined by self-report and medication use. Multivariate analyses of DM for PCa risk and grade were done using logistic regression. Moreover, we examined whether these associations were modified by the body mass index using subgroup analyses (nonobese Ͻ25 kg/m 2 or obese Ն25 kg/m 2) and interaction tests. Cancer grade was classified according to the Gleason score (GS): low-grade (GS Յ6), intermediate-grade (GS 7), and high-grade (GS 8-10). RESULTS Of 2038 patients, obesity and DM was observed in 606 (30%) and 213 (11%), respectively. Also, 836 patients (41%) had positive biopsy findings. On multivariate analysis, we found no significant association of DM with the risk of overall PCa (P ϭ .106) or the risk of low-grade (P ϭ .735), intermediate-grade (P ϭ .119), or high-grade (P ϭ .110) disease. When stratified by obesity, the relative risk (RR) of PCa detection for diabetic men apparently increased with higher cancer grade (low grade, RR ϭ 1.19, P ϭ .71; intermediate grade, RR ϭ 2.01, P ϭ .099; high-grade, RR ϭ 4.03, P ϭ .025). However, in the nonobese men, no association was noted between DM and PCa risk, irrespective of grade. Obesity modified the effect of DM on high-grade disease risk with a trend (P for interaction ϭ .087). CONCLUSION DM was associated with more aggressive PCa detection among Japanese obese patients with gray-zone PSA levels undergoing extended biopsy.

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

Diabetologia, 2016

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 sign...

Diabetes and Risk of Prostate Cancer

Diabetes Care, 2011

OBJECTIVE The link between diabetes and prostate cancer is rarely studied in Asians. RESEARCH DESIGN AND METHODS The trend of age-standardized prostate cancer incidence in 1995–2006 in the Taiwanese general population was calculated. A random sample of 1,000,000 subjects covered by the National Health Insurance in 2005 was recruited. A total of 494,630 men for all ages and 204,741 men ≥40 years old and without prostate cancer at the beginning of 2003 were followed to the end of 2005. Cumulative incidence and risk ratio between diabetic and nondiabetic men were calculated. Logistic regression estimated the adjusted odds ratios for risk factors. RESULTS The trend of prostate cancer incidence increased significantly (P < 0.0001). The cumulative incidence markedly increased with age in either the diabetic or nondiabetic men. The respective risk ratio (95% CI) for all ages and age 40–64, 65–74, and ≥75 years was 5.83 (5.10–6.66), 2.09 (1.60–2.74), 1.35 (1.07–1.71), and 1.39 (1.12–1.71...

Diabetes Mellitus and Prostate Cancer Risk; A Nationwide Case-Control Study within PCBaSe Sweden

Cancer Epidemiology Biomarkers & Prevention, 2013

Background: Diabetes mellitus (DM) increases the risk for cancer at almost all sites, but data on the association with prostate cancer are inconsistent. Methods: We assessed the risk of a prostate cancer diagnosis among men with type 2 (T2)DM in a nationwide population-based case-control study including 44,352 men with prostate cancer identified through the Prostate Cancer data Base Sweden (PCBaSe) between 2002 and 2006 and 221,495 age-matched men from the general population. Results: Overall, the risk of prostate cancer among men with T2DM was lower than among men without T2DM [OR, 0.80; 95% confidence interval (CI), 0.76-0.85]. The risk decreased with longer disease duration and was observed across all tumor risk categories, although most clearly among men with low risk tumors (OR, 0.71; 95% CI, 0.64-0.80). The risk for prostate cancer was reduced among diabetic men on dietary treatment only (OR, 0.89; 95% CI, 0.80-0.99) but more markedly among men on oral hypoglycemic agents (OR, 0.80; 95% CI, 0.74-0.87) and insulin (OR, 0.72; 95% CI, 0.69-0.81). Obese diabetic men (BMI > 30 kg/m 2) showed a reduced risk (OR, 0.72; 95% CI, 0.65-0.80) compared with men without diabetes. There was a trend of decreasing risk with increasing levels of HbA1c (P < 0.05). Conclusions: This nationwide study confirmed a reduced risk of being diagnosed with prostate cancer among men with T2DM, especially for low-risk tumors. An altered hormonal milieu is a plausible explanation, although the possibility of decreased prostate cancer detection among diabetic men cannot be ruled out. Impact: This is the largest study to examine the association between T2DM and prostate cancer accounting for tumor risk group and diabetes treatment. Cancer Epidemiol Biomarkers Prev; 22(6); 1102-9. Ó2013 AACR.

Obesity increases the risk for high-grade prostate cancer: results from the REDUCE study

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2014

Studies suggest that obesity is associated with lower risk of prostate cancer but more aggressive cancers. As obesity lowers PSA levels, these observations may be influenced by detection bias. We examined the association between obesity and risk of low- and high-grade prostate cancer in REDUCE, in which biopsies were largely independent of PSA. The REDUCE study tested dutasteride for prostate cancer risk reduction in men with a PSA of 2.5 to 10.0 ng/mL and a negative biopsy. Study participants included 6,729 men who underwent at least one on-study biopsy. The association between baseline body mass index (BMI <25 kg/m(2) normal weight; 25-29.9 kg/m(2) overweight; and ≥30 kg/m(2) obese) and risk of high-grade (Gleason ≥7) or low-grade prostate cancer (Gleason <7) versus no prostate cancer was examined using multinomial logistic regression. Overall, 1,739 men (27%) were normal weight, 3,384 (53%) overweight, and 1,304 (20%) were obese. Obesity was associated with lower risk of lo...

Diabetes mellitus and prostate cancer risk

Expert Review of Endocrinology & Metabolism, 2010

The relationship of diabetes mellitus with overall prostate cancer risk has been thoroughly evaluated in several large cohorts, including the Prostate, Lung, Colorectal and Ovarian trial and the NIH-American Association of Retired Persons study."

Diabetes mellitus and prostate cancer risk among older men: population-based case-control study

British journal of cancer, 2004

We investigate the relation between diabetes mellitus and risk of prostate cancer among older (age 65-79 years) men in a population-based case-control study of 407 incident histologically confirmed cases registered in the South Carolina Central Cancer Registry between 1999 and 2001 (70.6% response rate); controls were 393 men identified through the Health Care Financing Administration Medicare beneficiary file for South Carolina in 1999 (63.8% response rate). After adjusting for age, race, and prostate cancer screening in the past 5 years, a history of diabetes mellitus was associated with a reduced risk of prostate cancer (adjusted odds ratio (aOR)=0.64; 95% confidence interval (CI)=0.45, 0.91). The protective effect was stronger for those with complications associated with diabetes (aOR=0.61; 95% CI=0.42, 0.90) and for African-American men (aOR=0.36; 95% CI=0.21, 0.62). Additional research is needed to understand the biologic mechanisms by which diabetes may influence prostate can...