Abstract
CONTEXT: To date, established risk factors for prostate cancer (PCa) are limited to age, race, family history, and certain genetic polymorphisms. Despite great research efforts, available evidence on potentially modifiable risk factors is conflicting. Moreover, most studies on PCa risk factors did not consider the impact of prostate-specific antigen (PSA) testing on PCa diagnosis. OBJECTIVE: To provide a detailed overview of the latest evidence on the role of metabolic diseases, drugs, and dietary factors for risk of PCa incidence, recurrence, and survival in men exposed to PSA testing. EVIDENCE ACQUISITION: A systematic review of the English-language literature was performed using the MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science databases according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses recommendations. Randomized, case-control, or cohort studies published during the periods 2008-2017 (on drugs and metabolic diseases) and 2003-2017 (on dietary factors), with extensive follow-up (>/=8-10yr for studies on PCa risk; >/=2-5yr for studies on PCa recurrence, progression, and survival, depending on the review subtopic) and adjusting of the analyses, beyond established risk factors, for either rate of PSA testing (for risk analyses) or PCa stage and primary treatment (for survival analyses), were eligible for inclusion. EVIDENCE SYNTHESIS: Overall, 39 reports from 22 observational studies were included. Studies were heterogeneous regarding definitions of exposure or outcomes, length of follow-up, risk of bias, and confounding. For some risk factors, evidence was insufficient to assess potential effects, while for others there was no evidence of an effect. For selected risk factors, namely metformin, aspirin and statin use, diabetes, obesity, and specific dietary intakes, there was low-quality evidence of modest effects on PCa risk. CONCLUSIONS: Current evidence from long-term observational studies evaluating the effect of drugs, metabolic diseases, and dietary factors for PCa risk considering the impact of PSA testing is still not conclusive. Future research is needed to confirm the associations suggested by our review, exploring their potential biological explanations and selecting those risk factors most likely to trigger effective public health interventions. PATIENT SUMMARY: We reviewed the available studies published in the recent literature on the potential role of drugs, metabolic diseases, and food and dietary factors for the risk of prostate cancer, considering the impact of prostate-specific antigen testing on prostate cancer diagnosis. We found that for some factors data are currently insufficient to make definitive conclusions, while for others available studies seem to indicate an effect on the risk of prostate cancer.
