A burgeoning field of research has highlighted the role of the human microbiome in mediating a range of pathologies including obesity, metabolic syndrome, inflammatory disorders, and alterations in stress responses and behaviour. Furthermore, the progression of certain cancers may be driven by microbial interactions and possess distinct microbial signatures which may contribute towards tumour inflammation. The gut microbiome of an individual has potential to be modified in order to improve health outcomes given recent therapeutic developments.

Whilst observational epidemiological studies have provided evidence that the gut microbiome may play a role in cancer risk, such studies typically suffer forms of bias such as reverse causation and residual confounding. In recent years, Mendelian randomization has been increasingly utilised to unravel the connections between various exposures and cancer outcomes, using genetic variants as instruments for risk factors to overcome such biases. This technique is well-suited to analysing cancer due to a number of factors, including the long latency period of many cancers which makes reverse causation a common downfall of previous findings, as well as overcoming the time- and expense-related limitations of randomised controlled trials.

The hypothesis of this project is that the gastrointestinal microbiome is a causative factor in breast cancer incidence and progression. Key aims are to test this hypothesis with the use of epidemiological methods including Mendelian randomisation techniques to improve causality, utilising GWAS and individual-level data to investigate the associations between composition of the gut microbiome and the aetiology of breast cancer.