The association of diabetes with risk of prostate cancer defined by clinical and molecular features

Abstract

Background To prospectively examine the association between diabetes and risk of prostate cancer defined by clinical and molecular features. Methods A total of 49,392 men from the Health Professionals Follow-up Study (HPFS) were followed from 1986 to 2014. Data on self-reported diabetes were collected at baseline and updated biennially. Clinical features of prostate cancer included localised, advanced, lethal, low-grade, intermediate-grade, and high-grade. Molecular features included TMPRSS2: ERG and PTEN subtypes. Cox proportional hazards regression models were used to evaluate the association between diabetes and incidence of subtype-specific prostate cancer. Results During 28 years of follow-up, we documented 6733 incident prostate cancer cases. Relative to men free from diabetes, men with diabetes had lower risks of total (HR: 0.82, 95% CI: 0.75–0.90), localised (HR: 0.82, 95% CI: 0.74–0.92), low-and intermediate-grade prostate cancer (HR: 0.77, 95% CI: 0.66–0.90; HR: 0.77, 95% CI: 0.65–0.91, respectively). For molecular subtypes, the HRs for ERG-negative and ERG-positive cases were 0.63 (0.42–0.95) and 0.72 (0.46–1.12); and for PTEN-intact and PTEN-loss cases were 0.69 (0.48–0.98) and 0.52 (0.19–1.41), respectively. Conclusion Besides providing advanced evidence for the inverse association between diabetes and prostate cancer, this study is the first to report associations between diabetes and ERG/PTEN defined prostate cancers.

Serum proteomics links suppression of tumor immunity to ancestry and lethal prostate cancer

“…Included in this model were the 82 immune-oncology markers and 6 patient feature covariates (age, education, BMI, smoking history, aspirin use, and diabetes). Of those patient features, education as a surrogate for socioeconomic status and health care access, BMI, smoking status, and aspirin use have previously been associated with the risk of lethal prostate cancer whereas the direction and strength association for diabetes with prostate cancer and disease outcomes is more uncertain 31 , 32 . Utilizing this method, we could not identify a robust predictive signature of lethal prostate cancer for EA patients.…”

The Triple Health Threat of Diabetes, Obesity, and Cancer—Epidemiology, Disparities, Mechanisms, and Interventions

“…The joint and independent effects of obesity and diabetes on cancer risk may vary by race and ethnicity (38,48). Molecular pathological epidemiology studies have provided important mechanistic insights about how obesity and diabetes impact the molecular tumor characteristics (49) and how these tumor characteristics may vary by racial and ethnic subgroup (for example, black women are more likely than white women to be diagnosed with estrogen receptor negative and triple negative breast cancer, which are biologically more aggressive and have a poorer prognosis) (50).…”

The Influence of Anti-Diabetic Drugs on Prostate Cancer

“…Nonetheless, what is intriguing is the fact that several meta-analyses provide evidence supporting the fact that T2DM is correlated with reduced risk of incidence of prostate cancer [ 10 , 11 ]. One of the possible mechanisms which explains this inverse association between diabetes and PC, is the low insulin concentration in long-term diabetes, resulting in lower plasma IGF-1 levels in diabetics compared to non-diabetics [ 12 ]. Genetic links, especially hepatocyte nuclear factor-1 β gene (HNF1β), are also considered as a potential mechanism associated with the risk of both diabetes and PC.…”

“…Genetic links, especially hepatocyte nuclear factor-1 β gene (HNF1β), are also considered as a potential mechanism associated with the risk of both diabetes and PC. Although, for this inverse relationship, insufficient evidence has been reported [ 12 ]. Despite this reduction, diabetes mellitus increases mortality in many cancer types, including prostate cancer [ 13 , 14 ].…”