The research interests of the Complex Trait Genetics Team fall broadly into two categories: studying germline mediated breast cancer susceptibility; and understanding how genetic factors contribute to the heterogeneity often observed in inter-individual responses to drug treatments, particularly toxicities associated with chemotherapy.
We are currently conducting and developing research in three main areas:
Male Breast Cancer
Between 300-400 cases of male breast cancer are diagnosed every year in the UK, accounting for approximately 1% of new breast cancer diagnoses. Pathogenic mutations in BRCA2 account for about 10% of cases and the relative risks of breast cancer conferred by these mutations are significantly larger in men than women. We have recently demonstrated that this is also true for certain single nucleotide polymorphisms (SNPs). Using a combination of genotyping and next-generation sequencing we aim to identify additional common and rare genetic variants that influence risk of male breast cancer. Functional characterisation of novel loci will lead to new insights into breast cancer biology.
Pharmacogenetics is the study of germline genetic variation as it pertains to pharmacology, particularly in relation to efficacy and to toxicities associated with drug treatment. Genetic and environmental factors that influence pharmacokinetic and pharmacodynamic processes likely explain a significant proportion of the variation in treatment response and toxicity observed between patients receiving cancer treatment. Using samples and data collected from patients participating in clinical trials, we are conducting pharmacogenetic studies to identify genetic variants that influence drug metabolism and which may be predictive of toxicity and response to treatment.
Breast cancer intermediate phenotypes
Many intermediate phenotypes of relevance to breast cancer, for example mammographic density, have a significant heritable component. By reducing aetiological complexity, genetic analyses of breast cancer intermediate phenotypes should have increased power to detect trait associations. In particular, quantitative intermediate molecular phenotypes offer a powerful alternative to standard disease case-control studies. We have begun to explore the use of proteomic and metabolomic assays for the discovery and characterisation of putative breast cancer intermediate phenotypes in the Breakthrough Generations Study.