Abstract
BACKGROUND: The aim is to determine the effects of obesity and metformin-use in predicting prostate cancer (PC) risk. METHODS: We used male participants from the Sax Institute's 45 and Up Study (Australia), recruited between 2005-2009. Participants completed a questionnaire at recruitment which included information on self-reported body mass index (BMI; kg/m(2)). Participants' baseline data were linked by the Centre for Health Record Linkage to the NSW Cancer Registry and to Services Australia to identify index prescription claims for diabetic medications between January 2012 and December 2019. Multivariable Joint Cox regression analyses were used to examine associations between BMI, diabetic medications, and PC risk by cancer spread. RESULTS: Of the 94,674 eligible participants, there were 5265 incident PC cases (localised n = 2638, regional n = 925, metastatic n = 1514 and unknown; n = 1514) diagnosed between January 2012 and December 2019. BMI ≥ 30 kg/m(2) was associated with increased risk of metastatic PC (versus <30 kg/m(2); HR(adjusted) = 1.67;95%CI:1.10-2.54); metformin-use was associated with reduced risk of localised PC (versus non-users; HR(-metformin-only) = 0.65;95%CI:0.50-0.84; HR(metformin-combination) = 0.51;95%CI:0.34-0.77). Reduced risk of localised PC diagnosis in metformin-users (versus non-users) was evident across all BMI categories. CONCLUSION: Metformin-use in obese men is associated with reduced PC risk, if detected early. Further research could inform the repurposing of metformin for PC control.