Diabetes mellitus and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD 20892, USA.
Cancer Causes and Control (Impact Factor: 3.2). 07/2008; 19(10):1267-76. DOI: 10.1007/s10552-008-9198-6
Source: PubMed

ABSTRACT A history of diabetes has been fairly consistently related to a reduced prostate cancer risk, but previous investigations have not always addressed whether the relation with diabetes varies by prostate cancer aggressiveness or the association between diabetes and prostate cancer is modified by physical activity level and body mass, variables closely related to glucose metabolism.
We prospectively examined the diabetes-prostate cancer risk relationship among 33,088 men in the screening arm of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.
During 8.9 years follow-up, we ascertained 2,058 incident prostate cancer cases. Diabetes history was related to decreased risk of total prostate cancer (RR = 0.80, 95% CI = 0.68-0.95). The apparent protection afforded by diabetes was primarily due to the inverse relation with non-aggressive disease (i.e., the combination of low grade (Gleason sum <8) and low stage (clinical stages I or II); RR = 0.75; 95% CI = 0.62-0.91). In contrast, no association was noted between diabetes and aggressive disease (i.e., high grade or high stage (Gleason sum >or=8 or clinical stages III or IV); RR = 1.04, 95% CI = 0.74-1.45). In further analyses, the association between diabetes and aggressive prostate cancer was suggestively positive for men who were lean (RR = 1.64, 95% CI = 0.87-3.07; BMI < 25 kg/m(2)) and it was positive for men who were the most physically active (RR = 1.63; 95% CI = 1.07-2.62; 3+ hours vigorous activity/week). By comparison, no relations of diabetes to aggressive prostate cancer were noted for their heavier or physically less active counterparts (p-value for tests of interaction = 0.10 and 0.03 BMI and physical activity, respectively).
In this study, diabetes showed divergent relations with prostate cancer by tumor aggressiveness. Specifically, diabetes was inversely associated with early stage prostate cancer but it showed no relation with aggressive prostate cancer. Exploratory analyses suggested a positive association between diabetes and aggressive prostate cancer in the subgroup of men with a low BMI.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Diabetes mellitus and prostate cancer are two of the most important public health concerns, especially in elder population. Although diabetes has been recognized as a potent risk factor for many types of cancers, there is a large amount of evidence which shows that, it has a protective role against prostate cancer. The underlying cause of this protective role is not fully understood yet, however some mechanisms have been proposed in this area. In the present study we have reviewed these mechanisms and some new mechanisms are also proposed.
    Clinical Genitourinary Cancer 01/2014; · 1.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Metabolomic profiling has identified, sarcosine, a derivative of the amino acid glycine, as an important metabolite involved in the etiology or natural history of prostate cancer. We examined the association between serum sarcosine levels and risk of prostate cancer in 1,122 cases (813 non-aggressive and 309 aggressive) and 1,112 controls in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Sarcosine was quantified using high-throughput liquid chromatography-mass spectrometry. A significantly increased risk of prostate cancer was observed with increasing levels of sarcosine (Odds Ratio (OR) for the highest quartile of exposure (Q4) versus the lowest quartile (Q1) = 1.30, 95% CI: 1.02, 1.65; P-trend 0.03). When stratified by disease aggressiveness, we observed a stronger association for nonaggressive cases (OR for Q4 vs Q1 = 1.44, 95% CI: 1.11, 1.88; P-trend 0.006) but no association for aggressive prostate cancer (OR for Q4 vs Q1 = 1.03, 95% CI: 0.73, 1.47; P-trend 0.89). Although not statistically significant, temporal analyses showed a stronger association between sarcosine and prostate cancer for serum collected closer to diagnosis, suggesting that sarcosine may be an early biomarker of disease. Interestingly, the association between sarcosine and prostate cancer risk was stronger among men with diabetes (OR= 2.66, 95% CI: 1.04, 6.84) compared to those without reported diabetes (OR=1.23, 95% CI: 0.95-1.59, p-interaction=0.01). This study found that elevated levels of serum sarcosine are associated with an increased prostate cancer risk and evidence to suggest that sarcosine may be an early biomarker for this disease.
    Carcinogenesis 05/2013; · 5.64 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Diabetes is a serious metabolic disease that causes multiple organ dysfunctions. Recent evidence suggests that diabetes could contribute to the initiation and progression of certain cancers in addition to the classic diabetic complications. Furthermore, some of the drugs used clinically to treat patients with diabetes might affect cancer initiation, progression and mortality. The recent discovery of the possible anticancer effects of metformin, a classic antidiabetic drug, has led physicians and scientists to reconsider the interaction between diabetes and cancer. In the present review, we analyze recent reports in this field, and explore possible mechanistic links between diabetes and cancer biology.
    Journal of Diabetes Investigation. 02/2014;