Background
Metformin, a common prescription used to treat diabetes, can inhibit cancer growth. There is growing interest in exploring its chemo-preventative properties. The current study prospectively examined the association between metformin prescription and prostate cancer (PC) risk factors, in the diagnosis of aggressive PC.
Methods
Male participants were from Sax Institute’s 45 and Up Study (Australia) recruited between 2006-2009. Questionnaire and linked administrative health-data from the Centre for Health Record Linkage and Services Australia were used to identify incident PC, defined by a combined measure of Gleason grade group (GG) 1-5 and spread of disease (localized or advanced), healthcare utilisations, reimbursement records for Prostate Specific Antigen testing and metformin prescriptions (metformin-users). Multivariable Joint Cox regression analyses were used to examine associations between risk of PC diagnosis and its risk factors (first-degree PC family history, obesity (body mass index, BMI≥30 kg/m2), height (≥180cm)), in metformin-users (vers us non-users).
Results
Of 107,706 eligible men, there were 4,257 incident PC cases (median age 68.7 years) diagnosed between baseline recruitment and 31/12/2013. Of the 12,987 participants with a record for dispensing of metformin prescription, there were 315 incident PC cases. A multivariate Joint Cox regression analysis showed risk of PC diagnosis across all risk groups was reduced in metformin-users (versus non-users; HR<1) and increased in men with a first-degree PC family history (HR>1). Risk of advanced PC was increased in obese men (versus non-obese; HRadjusted=1.31;95%CI:1.01-1.69), and in men >180cm in height (versus<180cm; HRadjusted=1.36;95%CI:1.05-1.75). Stratified analyses by metformin-users (versus non-users) showed risk of advanced disease was no longer evident for these risk factors however, there was a reduced risk of localized PC in obese men (HRadjusted=0.63;95%CI:0.51-0.77) and men ≥180cm (HRadjusted=0.75;95%CI:0.61-0.93).
Conclusion
The reduced risk of localised and advanced PC was associated with metformin prescriptions. This adds to the growing body of evidence of the chemo-preventative properties of metformin warrants further investigation.