Dankner Rachel, Boffetta Paolo, Keinan-Boker Lital, Balicer Ran D, Berlin Alla, Olmer Liraz, Murad Havi, Silverman Barbara, Hoshen Moshe, Freedman Laurence S
Unit for Cardiovascular Epidemiology, The Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Tel Hashomer, 52621, Israel.
Sackler Faculty of Medicine, School of Public Health, Department of Epidemiology and Preventive Medicine, Tel Aviv University, Tel Aviv, Israel.
Diabetologia. 2016 Aug;59(8):1683-91. doi: 10.1007/s00125-016-3972-x. Epub 2016 May 17.
AIMS/HYPOTHESIS: 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).
CONCLUSIONS/INTERPRETATION: 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.
目的/假设：糖尿病与前列腺癌发病率之间一直呈现负相关。我们研究了糖尿病男性前列腺癌发病率较低是否归因于前列腺癌筛查模式导致的检测率降低。
我们对1034074名年龄在21 - 90岁、无癌症病史的以色列男性进行了一项基于人群的历史队列研究。根据糖尿病发病情况，对该队列在2002年至2012年期间进行随访，调整年龄、种族、社会经济地位和PSA检测后，观察前列腺特异性抗原（PSA）检测频率、平均PSA值及前列腺癌的检出情况。
2002年1月，74756名男性患有糖尿病。在11年的随访中，765483名（74%）男性仍未患糖尿病，193835名男性患了糖尿病。患糖尿病的男性进行PSA筛查的比例比未患糖尿病的男性高约10%，但患糖尿病男性的PSA阳性率（>4μg/l）低20%。在糖尿病诊断前3年，患糖尿病的男性PSA值就已显著低于未患糖尿病者。仅在低 - 中度分级肿瘤（Gleason评分2 - 6：调整后HR 0.83；95%CI 0.77, 0.89）中观察到新发糖尿病男性的前列腺癌风险降低。对于高级别肿瘤（Gleason评分7 - 10：HR 0.99；95%CI 0.88, 1.11）未观察到相关性。
结论/解读：我们的研究结果表明，糖尿病合并症是前列腺癌筛查策略中需要考虑的一个因素，特别是在解释PSA水平时。此外，我们证明糖尿病男性中低 - 中度分级而非高级别前列腺癌肿瘤的发病率降低，支持了低PSA水平而非较低肿瘤风险解释了观察到的糖尿病男性前列腺癌发病率降低这一可能性。
ClinicalTrials.gov NCT02072902。
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