Circulating adiponectin and leptin and risk of overall and aggressive prostate cancer: a systematic review and meta-analysis.

Obesity is associated with an increased risk of advanced, recurrent and fatal prostate cancer. Adipokines may mediate this relationship. We conducted a systematic review and meta-analysis of associations of leptin and adiponectin with overall and aggressive prostate cancer. Bibliographic databases were systematically searched up to 1st April 2017. Log Odds Ratios (ORs) per 2.5 unit increase in adiponectin or leptin levels were derived and pooled. All analyses were stratified by study type (cross-sectional/prospective). 746 papers were retrieved, 34 eligible studies identified, 31 of these could be included in the meta-analysis. Leptin was not consistently associated with overall prostate cancer (pooled OR 1.00, 95%CI 0.98-1.02, per 2.5 ng/ml increase, prospective study OR 0.97, 95%CI 0.95-0.99, cross-sectional study OR 1.19, 95%CI 1.13-1.26) and there was weak evidence of a positive association with aggressive disease (OR 1.03, 95%CI 1.00-1.06). There was also weak evidence of a small inverse association of adiponectin with overall prostate cancer (OR 0.96, 95%CI 0.93-0.99, per 2.5 µg/ml increase), but less evidence of an association with aggressive disease (OR 0.98, 95%CI 0.94-1.01). The magnitude of any effects are small, therefore levels of circulating adiponectin or leptin alone are unlikely to be useful biomarkers of risk or prognosis.

Associations of lifestyle factors and anthropometric measures with repeat PSA levels during active surveillance/monitoring.

BACKGROUND: Assessment of prostate-specific antigen increase with time (PSA growth) is a fundamental component of active surveillance among men with localized prostate cancer. Factors that influence PSA growth, however, are unclear. We evaluated associations of anthropometric and lifestyle factors with age-related PSA growth. METHODS: Repeat PSA measures from 404 men, aged 50 to 69 years, with localized prostate cancer undergoing active monitoring were obtained. From log(PSA) measures, age-specific multilevel mixed effect linear models were developed to predict PSA at age 50 years and yearly increase in postdiagnosis PSA. Baseline anthropometric measures, alcohol consumption, occupational class, smoking status, and physical activity were added to the model as covariates. RESULTS: The median number of repeat PSAs was 13 (range, 2-40), and the mean duration of follow-up was 4.8 years (SD, 2.3). The basic model of age-related PSA growth in men with localized prostate cancer estimated a mean PSA at age 50 of 3.95 ng/mL [95% confidence interval (CI): 3.55 to 4.39] and a yearly increase of 8.50% (95% CI: 7.90% to 9.10%). PSA at age 50 years was 2.1% lower per unit increase in weighted exercise score (95% CI: -3.3 to -0.8), 5.3% lower per 5 cm increase in height (95% CI: -9.4 to -1.1), and 24.5% higher (95% CI: 4.0 to 49.1) in current smokers than never smokers. Similar associations with PSA growth were seen. CONCLUSION: Smoking and exercise are modifiable lifestyle factors that may be associated with PSA levels in men with localized prostate cancer undergoing active monitoring/surveillance. IMPACT: These factors may be useful in understanding etiology of progression.

Metabolic imbalance and prostate cancer progression.

There is substantial evidence implicating environmental factors in the progression of prostate cancer. The metabolic consequences of a western lifestyle, such as obesity, insulin resistance and abnormal hormone production have been linked to prostate carcinogenesis through multiple overlapping pathways. Insulin resistance results in raised levels of the mitogens insulin and insulin-like growth factor-1, both of which may affect prostate cancer directly, or through their effect on other metabolic regulators. Obesity is associated with abnormal levels of adipocyte-derived peptides (adipokines), sex hormones and inflammatory cytokines. Adipokines have been shown to influence prostate cancer in both cell culture studies and observational, population level studies. Testosterone appears to have a complex relationship with prostate carcinogenesis, and it has been suggested that the lower levels associated with obesity may select for more aggressive androgen independent prostate cancer cells. Prostatic inflammation, caused by infection, urinary reflux or dietary toxins, frequently occurs prior to cancer development and may influence progression to advanced disease. High levels of ω-6 fatty acids in the diet may lead to the production of further inflammatory molecules that may influence prostate cancer. Increased fatty acid metabolism occurs within tumour cells, providing a potential target for prostate cancer therapies. Aberrations in amino acid metabolism have also been identified in prostate cancer tissue, particularly in metastatic cancer. This evidence indicates lifestyle interventions may be effective in reducing the incidence of clinical disease. However, much more research is needed before recommendations are made.