ABSTRACTBackgroundBreast and prostate cancer are the first and second most common types of cancer in women and men, respectively. A recent campaign by Cancer Research UK emphasised obesity as being a causal risk factor for cancer, although previously published evidence is heterogenous. We aimed to explore the causal effect of adiposity on breast and prostate cancer risk in the UK Biobank (UKB), a large prospective cohort study, and published data.MethodsWe used Mendelian randomisation (MR) to assess the causal effect of body mass index (BMI), body fat percentage (BFP), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) on breast and prostate cancer risk.ResultsWe obtained estimates (odds ratios, OR, per SD unit increase) of the causal effect of the adiposity measures on breast and prostate cancer risk. BMI and HC decrease the risk of breast cancer (OR 0.776 [95% CIs 0.661-0.91] and OR 0.781 [95% CIs 0.649-0.94], respectively). WC, BFP, and BMI decrease the risk of prostate cancer (OR 0.602 [95% CIs 0.439-0.825], OR 0.629 [95% CIs 0.414-0.956], and OR 0.695 [95% CIs 0.553-0.874], respectively). The protective effect of adiposity on prostate cancer risk is enhanced in men who are exposed to potentially hazardous substances at work, and the association between BMI and breast cancer is confounded by variables associated with general health.ConclusionsIn conclusion, increasing adiposity is causally protective for breast and prostate cancer and the effects in prostate cancer may, at least partly, be due to the safe storage of chemicals in adipose cells. It is necessary to explore the mechanisms through which adiposity may protect against or be a risk factor for cancer, to identify how the latter can be minimised without sacrificing the former, and to base public health campaigns around sound evidence.HIGHLIGHTSPreviously published evidence regarding the effect of adiposity on prostate and breast cancer risk is heterogenousIncreasing BMI and hip circumference decrease the risk of breast cancer in womenIncreasing waist circumference, body fat percentage, and BMI decrease the risk of prostate cancerThe protective effect of adiposity on prostate cancer is stronger in men who are exposed to carcinogens at workPublic health campaigns need to target the negative aspects of adiposity whilst preserving the positive aspects
O6-2.5 Alcohol and prostate cancer risk: a mendelian randomisation approach