PhD Confirmation Seminar - Explaining the Causal Effect of Obesity on Risk of Colorectal and Postmenopausal Breast Cancer: an assessment of mediation and interaction, Dr Ghazaleh Dashti

Excess body weight causes colorectal cancer and postmenopausal breast cancer. In Australia, 2000 cases per year of these cancers are attributable to obesity. Targeting biological markers that mediate or modify the effect of obesity on cancer offers great promise for primary prevention and early detection. However, before this is possible, a greater understanding of the postulated biological pathways is essential.

Chronic inflammation and abnormal production of adipocytokines, insulin resistance, and disturbances to sex-steroid hormones are the postulated pathways through which obesity could cause colorectal and postmenopausal breast cancer. Few epidemiological studies have attempted to assess these pathways simultaneously and even fewer have performed causal mediation analysis to quantify the relative contributions of the pathways.

In this PhD, these pathways will be comprehensively explored using already collected data from subset studies of three large prospective cohort studies, the Melbourne Collaborative Cohort Study, the European Prospective Investigation into Cancer and Nutrition, and the Women’s Health Initiative Observational Study. Causal mediation analyses will be performed to estimate the effects through the mediator (indirect effect) and not through the mediator (direct effect) and obesity-biomarker interactions will be estimated.

Supervisors: Prof Dallas English, Prof Julie Simpson, Dr Emily Karahalios